protease inhibitors


Summary: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).

Top Publications

  1. doi Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b-infected null responders
    Kazuaki Chayama
    Hiroshima University, Hiroshima, Japan
    Hepatology 55:742-8. 2012
  2. ncbi Targeting proteases: successes, failures and future prospects
    Boris Turk
    Department of Biochemistry and Molecular Biology, J Stefan Institute, Jamova 39, SI 1000 Ljubljana, Slovenia
    Nat Rev Drug Discov 5:785-99. 2006
  3. doi Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus-infected patients
    Simone Susser
    JW Goethe University Hospital, Frankfurt, Germany
    Hepatology 50:1709-18. 2009
  4. ncbi Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir
    Christoph Sarrazin
    Klinik fur Innere Medizin II, Universitat des Saarlandes, Homburg Saar, Germany
    Gastroenterology 132:1767-77. 2007
  5. doi Hepatitis C virus resistance to protease inhibitors
    Philippe Halfon
    Virological Departement Laboratoire Alphabio, Hopital Ambroise Pare, Marseille, France
    J Hepatol 55:192-206. 2011
  6. doi Differential efficacy of protease inhibitors against HCV genotypes 2a, 3a, 5a, and 6a NS3/4A protease recombinant viruses
    Judith M Gottwein
    Copenhagen Hepatitis C Program CO HEP, Department of Infectious Diseases and Clinical Research Centre, Copenhagen University Hospital, Hvidovre and Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
    Gastroenterology 141:1067-79. 2011
  7. doi Proteasome inhibitors in cancer therapy: lessons from the first decade
    Robert Z Orlowski
    Department of Lymphoma Myeloma, Division of Cancer Medicine, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 14:1649-57. 2008
  8. pmc Naturally occurring dominant resistance mutations to hepatitis C virus protease and polymerase inhibitors in treatment-naïve patients
    Thomas Kuntzen
    Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Hepatology 48:1769-78. 2008
  9. ncbi Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy
    Christopher M Overall
    University of British Columbia Centre for Blood Research, CBCRA Program in Breast Cancer Metastasis, Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
    Nat Rev Cancer 6:227-39. 2006
  10. doi Antiviral strategies in hepatitis C virus infection
    Christoph Sarrazin
    Klinikum der JW Goethe Universität, Medizinische Klinik 1, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany
    J Hepatol 56:S88-100. 2012

Detail Information

Publications365 found, 100 shown here

  1. doi Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b-infected null responders
    Kazuaki Chayama
    Hiroshima University, Hiroshima, Japan
    Hepatology 55:742-8. 2012
    ..There was no viral breakthrough. Diarrhea and headache, generally mild, were the most common adverse events; transaminase elevations were reported in 3 patients, but did not result in discontinuation...
  2. ncbi Targeting proteases: successes, failures and future prospects
    Boris Turk
    Department of Biochemistry and Molecular Biology, J Stefan Institute, Jamova 39, SI 1000 Ljubljana, Slovenia
    Nat Rev Drug Discov 5:785-99. 2006
    ..The status of human protease research and prospects for future protease-targeted drugs are reviewed here, with reference to some key examples where protease drugs have succeeded or failed...
  3. doi Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus-infected patients
    Simone Susser
    JW Goethe University Hospital, Frankfurt, Germany
    Hepatology 50:1709-18. 2009
    ..Mathematical modeling revealed impaired replicative fitness for all single mutations, whereas for combined mutations a relative increase of replication efficiency was suggested...
  4. ncbi Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir
    Christoph Sarrazin
    Klinik fur Innere Medizin II, Universitat des Saarlandes, Homburg Saar, Germany
    Gastroenterology 132:1767-77. 2007
    ..4A protease inhibitor, has shown strong antiviral activity in phase 1 clinical studies. Because of high levels of HCV replication and the low fidelity of HCV polymerase, selection of resistant isolates during therapy may occur...
  5. doi Hepatitis C virus resistance to protease inhibitors
    Philippe Halfon
    Virological Departement Laboratoire Alphabio, Hopital Ambroise Pare, Marseille, France
    J Hepatol 55:192-206. 2011
    ..different pathways of resistance profiles based on the chemical scaffold (linear or macrocyclic) of the protease inhibitors have been described...
  6. doi Differential efficacy of protease inhibitors against HCV genotypes 2a, 3a, 5a, and 6a NS3/4A protease recombinant viruses
    Judith M Gottwein
    Copenhagen Hepatitis C Program CO HEP, Department of Infectious Diseases and Clinical Research Centre, Copenhagen University Hospital, Hvidovre and Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
    Gastroenterology 141:1067-79. 2011
    The hepatitis C virus (HCV) genotype influences efficacy of interferon (IFN)-based therapy. HCV protease inhibitors are being licensed for treatment of genotype 1 infection...
  7. doi Proteasome inhibitors in cancer therapy: lessons from the first decade
    Robert Z Orlowski
    Department of Lymphoma Myeloma, Division of Cancer Medicine, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 14:1649-57. 2008
    ..This saga provides a salient example of the promise of translational medicine and a paradigm by which other agents may be successfully brought from the bench to the bedside...
  8. pmc Naturally occurring dominant resistance mutations to hepatitis C virus protease and polymerase inhibitors in treatment-naïve patients
    Thomas Kuntzen
    Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Hepatology 48:1769-78. 2008
    Resistance mutations to hepatitis C virus (HCV) nonstructural protein 3 (NS3) protease inhibitors in <1% of the viral quasispecies may still allow >1000-fold viral load reductions upon treatment, consistent with their reported ..
  9. ncbi Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy
    Christopher M Overall
    University of British Columbia Centre for Blood Research, CBCRA Program in Breast Cancer Metastasis, Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3
    Nat Rev Cancer 6:227-39. 2006
    ..These effects might partially account for the failure of MMP inhibitors in clinical trials. What are the major challenges in MMP target validation and MMP-inhibitor-drug development?..
  10. doi Antiviral strategies in hepatitis C virus infection
    Christoph Sarrazin
    Klinikum der JW Goethe Universität, Medizinische Klinik 1, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany
    J Hepatol 56:S88-100. 2012
    ..Two NS3/4A protease inhibitors, telaprevir and boceprevir, were approved in Europe and the United States in 2011 in combination with ..
  11. ncbi Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells
    Jian Zhong Qin
    Department of Pathology, Loyola University Medical Center, Maywood, Illinois 60153 5385, USA
    Cancer Res 65:6282-93. 2005
  12. doi Efficacy of the protease inhibitor BI 201335, polymerase inhibitor BI 207127, and ribavirin in patients with chronic HCV infection
    Stefan Zeuzem
    J W Goethe University Hospital, Frankfurt, Germany
    Gastroenterology 141:2047-55; quiz e14. 2011
    ..We investigated the antiviral effect and safety of BI 201335 (an inhibitor of the NS3/4A protease) and BI 207127 (an inhibitor of the NS5B non-nucleoside polymerase) with ribavirin...
  13. ncbi Roles of naturally occurring protease inhibitors in the modulation of host cell signaling and cellular invasion by Trypanosoma cruzi
    Julio Scharfstein
    Lnstituto de Biofisica Carlos Chagas Filho, UFRJ, Rio de Janeiro, Brazil
    Subcell Biochem 47:140-54. 2008
    ..In conclusion, the studies reviewed herein illustrate how regulation of parasite proteases may affect host-parasite equilibrium in the course of IT cruzi infection...
  14. ncbi Changing views of the role of matrix metalloproteinases in metastasis
    A F Chambers
    Department of Oncology, University of Western Ontario, and London Regional Cancer Centre, Canada
    J Natl Cancer Inst 89:1260-70. 1997
    ..Further clarification of the mechanisms by which MMPs regulate growth of primary and metastatic tumors will be important in the development of novel therapeutic strategies against metastases...
  15. doi Discovery and development of telaprevir: an NS3-4A protease inhibitor for treating genotype 1 chronic hepatitis C virus
    Ann D Kwong
    Vertex Pharmaceuticals, Cambridge, Massachusetts, USA
    Nat Biotechnol 29:993-1003. 2011
    ..Lessons learned from the development of telaprevir suggest that makers of innovative medicines cannot rely solely on traditional drug discovery metrics, but must develop innovative, scientifically guided pathways for success...
  16. doi The proprotein convertases, 20 years later
    Nabil G Seidah
    Biochemical Neuroendocrinology Laboratory, Clinical Research Institute of Montreal, Montreal, QC, Canada H2W 1R7
    Methods Mol Biol 768:23-57. 2011
    ..3.2) implicated in health and disease, which traffic through the cells via multiple sorting pathways (Fig. 3.3)...
  17. doi Identification of proteases that regulate erythrocyte rupture by the malaria parasite Plasmodium falciparum
    Shirin Arastu-Kapur
    Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, USA
    Nat Chem Biol 4:203-13. 2008
    ..chemical genetic screen using a highly focused library of more than 1,200 covalent serine and cysteine protease inhibitors to identify compounds that block host cell rupture by P. falciparum...
  18. doi The emerging roles of serine protease cascades in the epidermis
    Petra Ovaere
    Department of Biomedical Molecular Biology, Ghent University, Belgium
    Trends Biochem Sci 34:453-63. 2009
    ..Therefore, a deeper knowledge of the regulation of these serine protease cascades could form the basis for development of appropriate treatments for skin disorders such as Netherton syndrome...
  19. pmc Differential timing of spider mite-induced direct and indirect defenses in tomato plants
    Merijn R Kant
    Institute for Biodiversity and Ecosystem Dynamics, Department of Plant Physiology, University of Amsterdam, 1098 SM Amsterdam, The Netherlands
    Plant Physiol 135:483-95. 2004
    ..Our results indicate that tomato activates its indirect defenses (volatile production) to complement the direct defense response against spider mites...
  20. doi Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells
    Frederic Colland
    Hybrigenics Pharma, 75014 Paris, France
    Mol Cancer Ther 8:2286-95. 2009
    ..We thus report the identification of the first lead-like inhibitor against USP7, providing a structural basis for the development of new anticancer drugs...
  21. pmc Plasma metabolomics identifies lipid abnormalities linked to markers of inflammation, microbial translocation, and hepatic function in HIV patients receiving protease inhibitors
    Edana Cassol
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA 02215, USA
    BMC Infect Dis 13:203. 2013
    ..Metabolic abnormalities are common in HIV-infected individuals on antiretroviral therapy (ART), but the biochemical details and underlying mechanisms of these disorders have not been defined...
  22. ncbi Aspartic protease inhibitors as potential anti-Candida albicans drugs: impacts on fungal biology, virulence and pathogenesis
    L A Braga-Silva
    Departamento de Microbiologia Geral, Instituto de Microbiologia Prof Paulo de Góes and Programa de Pós Graduação em Bioquímica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
    Curr Med Chem 18:2401-19. 2011
    ..albicans drugs. Herein, we review the beneficial properties of pepstatin A and aspartic-type protease inhibitors used in the anti-human immunodeficiency virus chemotherapy on C...
  23. pmc Drug resistance against HCV NS3/4A inhibitors is defined by the balance of substrate recognition versus inhibitor binding
    Keith P Romano
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Proc Natl Acad Sci U S A 107:20986-91. 2010
    ..Resistance against the most promising protease inhibitors, telaprevir, boceprevir, and ITMN-191, has emerged in clinical trials...
  24. doi Protease inhibitors for the treatment of chronic hepatitis C genotype-1 infection: the new standard of care
    Brian L Pearlman
    Center For Hepatitis C, Atlanta Medical Center, Atlanta, GA 30309, USA
    Lancet Infect Dis 12:717-28. 2012
    ..With US Food and Drug Administration approval of boceprevir and telaprevir--two protease inhibitors--the standard-of-care treatment for genotype-1 infection, the main genotype worldwide, is now peginterferon ..
  25. pmc Development of protease inhibitors for protozoan infections
    James H McKerrow
    Department of Pathology, University of California San Francisco, 1700 4th Street, San Francisco, CA 94158 2330, USA
    Curr Opin Infect Dis 21:668-72. 2008
    ..These roles include processing of host or parasite surface proteins for invasion of host cells, digestion of host proteins for nutrition, and inactivation of host immune defense mediators...
  26. doi New HCV therapies on the horizon
    J Vermehren
    Medizinische Klinik 1, Klinikum der J W Goethe Universitat, Frankfurt am Main, Germany
    Clin Microbiol Infect 17:122-34. 2011
    ..Monotherapy with protease inhibitors has shown high antiviral activity, but is associated with frequent selection of resistant HCV variants, ..
  27. ncbi Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases
    Jialiang Hu
    Rega Institute for Medical Research, Catholic University of Leuven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    Nat Rev Drug Discov 6:480-98. 2007
  28. pmc PLANT-PIs: a database for plant protease inhibitors and their genes
    F De Leo
    Dipartimento di Biochimica e Biologia Molecolare, Universita di Bari, Via Amendola 165 A, Bari, Italy
    Nucleic Acids Res 30:347-8. 2002
    PLANT-PIs is a database developed to facilitate retrieval of information on plant protease inhibitors (PIs) and related genes...
  29. ncbi The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells
    T Hideshima
    Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer Res 61:3071-6. 2001
    ..Given the acceptable animal and human toxicity profile of PS-341, these studies provide the framework for clinical evaluation of PS-341 to improve outcome for patients with this universally fatal hematological malignancy...
  30. ncbi Bortezomib or high-dose dexamethasone for relapsed multiple myeloma
    Paul G Richardson
    Dana Farber Cancer Institute, Boston, MA 02115, USA
    N Engl J Med 352:2487-98. 2005
    ..This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies...
  31. pmc Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss
    Elisabeth Dam
    INSERM U552, Paris, France
    PLoS Pathog 5:e1000345. 2009
    Human immunodeficiency virus type 1 (HIV-1) resistance to protease inhibitors (PI) results from mutations in the viral protease (PR) that reduce PI binding but also decrease viral replicative capacity (RC)...
  32. pmc Cleavage of influenza virus hemagglutinin by airway proteases TMPRSS2 and HAT differs in subcellular localization and susceptibility to protease inhibitors
    Eva Böttcher-Friebertshäuser
    Institute of Virology, Philipps University Marburg, Hans Meerwein Strasse 2, 35043 Marburg, Germany
    J Virol 84:5605-14. 2010
    ..iii) cleavage activation of HA and virus spread in TMPRSS2- and HAT-expressing cells can be suppressed by peptide mimetic protease inhibitors. The further development of these inhibitors could lead to new drugs for influenza treatment.
  33. pmc In vitro resistance profile of the hepatitis C virus NS3/4A protease inhibitor TMC435
    Oliver Lenz
    Tibotec BVBA, Mechelen, Belgium
    Antimicrob Agents Chemother 54:1878-87. 2010
    ..Finally, combinations of TMC435 with alpha interferon and NS5B polymerase inhibitors prevented the formation of drug-resistant replicon colonies...
  34. doi Resistance to anti-HCV protease inhibitors
    Alexander J Thompson
    St Vincent s Hospital Melbourne, Fitzroy, Victoria, Australia
    Curr Opin Virol 1:599-606. 2011
    The era of direct acting antiviral therapy for HCV infection has dawned with the recent approval of the NS3 protease inhibitors telaprevir and boceprevir...
  35. ncbi Pathogenesis of COPD. Part I. The role of protease-antiprotease imbalance in emphysema
    R T Abboud
    Division of Respiratory Medicine, Department of Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada
    Int J Tuberc Lung Dis 12:361-7. 2008
  36. doi Telaprevir versus boceprevir in chronic hepatitis C: a meta-analysis of data from phase II and III trials
    Mugdha Sitole
    Massachusetts College of Pharmacy and Health Sciences, Worcester, MA 01608, USA
    Clin Ther 35:190-7. 2013
    Telaprevir and boceprevir are protease inhibitors now added to therapy for patients with chronic hepatitis C virus (HCV) genotype 1 infection who either are treatment naive or have a history of relapse or recurrence following a previous ..
  37. doi WAP domain proteins as modulators of mucosal immunity
    Thomas S Wilkinson
    Institute of Life Science, Microbiology and Infection, Floor 5, School of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK
    Biochem Soc Trans 39:1409-15. 2011
    ..After providing information about the 'classical' antiproteasic role of these molecules, we will discuss the evidence pertaining to their pleiotropic functions in inflammation and immunity...
  38. ncbi Matrix metalloproteinase inhibitors and cancer: trials and tribulations
    Lisa M Coussens
    Department of Pathology and Cancer Research Institute, University of California, 2340 Sutter Street, San Francisco, CA 94143, USA
    Science 295:2387-92. 2002
    ..The important lessons learned from the MPI experience may be of great value for future studies of MPIs and for cancer drug development in general...
  39. ncbi Trypsin inhibitory loop is an excellent lead structure to design serine protease inhibitors and antimicrobial peptides
    Jianxu Li
    Biotoxin Unit of Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China
    FASEB J 21:2466-73. 2007
    ..Furthermore, functional analysis and a precursor comparison suggest that serine protease inhibitors may have a common ancestor with antimicrobial peptides.
  40. doi Conformational stabilization of ubiquitin yields potent and selective inhibitors of USP7
    Yingnan Zhang
    Department of Early Discovery Biochemistry, Genentech Inc, San Francisco, California, USA
    Nat Chem Biol 9:51-8. 2013
  41. doi Serum levels of IgG antibodies against oxidized LDL and atherogenic indices in HIV-1-infected patients treated with protease inhibitors
    Joel da Cunha
    Laboratory of Genetics and Molecular Hematology, University of Sao Paulo Medical School HCFMUSP, Sao Paulo, Brazil
    Clin Chem Lab Med 51:371-8. 2013
    ..In individuals infected with human immunodeficiency virus type 1 (HIV-1) with or without therapy, dyslipidemia and increased cardiovascular risk are observed...
  42. pmc Treatment of chronic hepatitis C virus infection in Japan: update on therapy and guidelines
    Kazuaki Chayama
    Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan
    J Gastroenterol 48:1-12. 2013
    ..Other protease inhibitors with fewer side effects are now in clinical trials in Japan...
  43. doi Mutations in hepatitis C virus NS3 protease domain associated with resistance to specific protease inhibitors in antiviral therapy naïve patients
    Allan Peres-da-Silva
    Viral Hepatitis Laboratory, Oswaldo Cruz Foundation, FIOCRUZ, Rua Leopoldo Bulhoes 1480, Rio de Janeiro, CEP 21041 210, Brazil
    Arch Virol 155:807-11. 2010
    The prevalence of naturally occurring mutations in hepatitis C virus associated with resistance to protease inhibitors in chronically infected patients has not been reported in Brazil...
  44. ncbi The plant proteolytic machinery and its role in defence
    Renier A L van der Hoorn
    Laboratory of Phytopathology, Wageningen University, 6709 PD, Wageningen, The Netherlands
    Curr Opin Plant Biol 7:400-7. 2004
    ..These exciting recent reports are probably just the first examples of what lies beneath. More roles for plant proteases in defence, as well as the regulation and substrates of these enzymes, are waiting to be discovered...
  45. doi Hepatitis C treatment highlights from the 2011 American Association for the Study of Liver Disease meeting
    Curtis Cooper
    Department of Medicine, Division of Infectious Diseases, University of Ottawa, Canada
    Clin Infect Dis 55:418-25. 2012
    ..Expertise in HCV antiviral resistance, drug metabolism, and drug-drug interactions and optimization of drug adherence are now key requirements in the DAA era...
  46. doi Natural prevalence of hepatitis C virus variants with decreased sensitivity to NS3.4A protease inhibitors in treatment-naive subjects
    Doug J Bartels
    Department of Infectious Diseases, Vertex Pharmaceuticals, Inc, Cambridge, Massachusetts 02139, USA
    J Infect Dis 198:800-7. 2008
    ..and clinical implications of naturally occurring variants that are resistant to hepatitis C virus (HCV) protease inhibitors in treatment-naive patients has not been reported...
  47. doi Functional peptidomics of amphibian skin secretion: A novel Kunitz-type chymotrypsin inhibitor from the African hyperoliid frog, Kassina senegalensis
    Hui Wang
    Natural Drug Discovery group, School of Pharmacy, Queen s University, Belfast BT9 7BL, Northern Ireland, UK
    Biochimie 94:891-9. 2012
    ..Among the components of these secretory peptidomes is an array of protease inhibitors. Inhibitors of trypsin are of widespread occurrence in different taxa and are representative of many ..
  48. ncbi A mathematical model for the roles of pericytes and macrophages in the initiation of angiogenesis. I. The role of protease inhibitors in preventing angiogenesis
    H A Levine
    Department of Mathematics, Iowa State University, Ames 50011, USA
    Math Biosci 168:77-115. 2000
    ..A second mechanism for the production of protease inhibitor from angiostatin by endothelial cells is proposed to be of Michaelis-Menten type. Mathematically, this mechanism includes the former as a subcase...
  49. pmc Susceptibility of treatment-naive hepatitis C virus (HCV) clinical isolates to HCV protease inhibitors
    Andrew Bae
    Department of Clinical Virology, Gilead Sciences, 333 Lakeside Dr, Foster City, CA 94404, USA
    Antimicrob Agents Chemother 54:5288-97. 2010
    In order to assess the natural variation in susceptibility to hepatitis C virus (HCV) NS3 protease inhibitors (PIs) among untreated HCV patient samples, the susceptibilities of 39 baseline clinical isolates were determined using a ..
  50. doi A new multigene superfamily of Kunitz-type protease inhibitors from sea anemone Heteractis crispa
    Marina P Isaeva
    Far Eastern Branch of Russian Academy of Sciences, Primorskiy kray, Vladivostok, Russian Federation
    Peptides 34:88-97. 2012
    Despite a considerable number of publications devoted to isolation and physicochemical properties of protease inhibitors from sea anemones, virtually nothing is known about the structure of the genes, and the nature of their isoforms ..
  51. pmc Ectodomain shedding of epidermal growth factor receptor ligands is required for keratinocyte migration in cutaneous wound healing
    S Tokumaru
    Department of Biochemistry, Osaka University Medical School, Suita, Osaka 565 0871, Japan
    J Cell Biol 151:209-20. 2000
    ..These findings indicate that the shedding of EGFR ligands represents a critical event in keratinocyte migration, and suggest their possible use as an effective clinical treatment in the early phases of wound healing...
  52. doi Protein digestion in cereal aphids (Sitobion avenae) as a target for plant defence by endogenous proteinase inhibitors
    Prashant Pyati
    School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, United Kingdom
    J Insect Physiol 57:881-91. 2011
  53. ncbi Protease inhibitors from several classes work synergistically against Callosobruchus maculatus
    Bahagiawati Amirhusin
    Indonesia Center for Agricultural Biotechnology and Genetic Resources Research and Development, Jalan Tentara Pelajar 3A, Bogor 16111, Indonesia
    J Insect Physiol 53:734-40. 2007
    ..We therefore explored possible interactions of three antimetabolic protease inhibitors fed to cowpea bruchids in artificial diets, using a recombinant soybean cysteine protease inhibitor scN, an ..
  54. pmc Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells
    Teru Hideshima
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 114:1046-52. 2009
    ..Moreover, IKKbeta inhibitors enhanced bortezomib-induced cytotoxicity. Our studies therefore suggest that bortezomib-induced cytotoxicity cannot be fully attributed to inhibition of canonical NF-kappaB activity in MM cells...
  55. ncbi Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic response to Bortezomib, a novel proteasome inhibitor, in human H460 non-small cell lung cancer cells
    Yi He Ling
    Department of Oncology, Albert Einstein College of Medicine, Bronx, New York 10461, USA New York University Cancer Institute, School of Medicine, New York University, New York, New York 10016, USA
    J Biol Chem 278:33714-23. 2003
    ..Thus ROS generation plays a critical role in the initiation of the bortezomib-induced apoptotic cascade by mediation of the disruption of Delta psi m and the release of cytochrome c from mitochondria...
  56. ncbi NOTCH signaling as a novel cancer therapeutic target
    L Miele
    Cutaneous Oncology Program, Cardinal Bernardin Cancer Center and Departments of Pathology and Microbiology Immunology, Loyola University Chicago, Maywood, IL 60153, USA
    Curr Cancer Drug Targets 6:313-23. 2006
    ..This review summarizes the evidence linking NOTCH signaling to several types of cancer, as well as the possible therapeutic indications of NOTCH inhibitors and the challenges facing their clinical development...
  57. ncbi Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341
    Teru Hideshima
    Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Blood 101:1530-4. 2003
    ..Inhibition of JNK activity abrogates PS-341-induced MM cell death. These studies identify molecular targets of PS-341 and provide the rationale for the development of second-generation, more targeted therapies...
  58. ncbi Proteasome inhibitors: from research tools to drug candidates
    A F Kisselev
    Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA
    Chem Biol 8:739-58. 2001
  59. ncbi Proteases in parasitic diseases
    James H McKerrow
    Department of Pathology, Sandler Center, University of California, San Francisco, California 94143, USA
    Annu Rev Pathol 1:497-536. 2006
  60. ncbi The neprilysin (NEP) family of zinc metalloendopeptidases: genomics and function
    A J Turner
    School of Biochemistry and Molecular Biology, University of Leeds, Leeds, UK
    Bioessays 23:261-9. 2001
    ..These model organisms also provide convenient systems for examining cell-specific expression, developmental and functional roles of this peptidase family, and reveal the power of functional genomics...
  61. ncbi Assessment of atherosclerosis using carotid ultrasonography in a cohort of HIV-positive patients treated with protease inhibitors
    E Seminari
    Department of Infectious Diseases, IRCCS, Policlinico S Matteo, 27100, Pavia, Italy
    Atherosclerosis 162:433-8. 2002
    Lipid disorders associated with the use of protease inhibitors (PI) may be a risk factor for premature atherosclerosis development...
  62. pmc Matrix metalloproteinase-induced epithelial-mesenchymal transition in breast cancer
    Evette S Radisky
    Mayo Clinic Cancer Center, Griffin Building, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    J Mammary Gland Biol Neoplasia 15:201-12. 2010
    ..We also suggest approaches to inhibit these MMP-mediated malignant processes for therapeutic benefit...
  63. pmc A locus on human chromosome 20 contains several genes expressing protease inhibitor domains with homology to whey acidic protein
    Adam Clauss
    Wallenberg Laboratory, Department of Laboratory Medicine, University Hospital MAS, Lund University, S 205 02 Malmo, Sweden
    Biochem J 368:233-42. 2002
    ..1. Among them are genes of the known or postulated protease inhibitors elafin, secretory leucocyte protease inhibitor, human epididymis gene product 4, eppin, and huWAP2...
  64. ncbi Interactions of proteases, protease inhibitors, and the beta1 integrin/laminin gamma3 protein complex in the regulation of ectoplasmic specialization dynamics in the rat testis
    Michelle K Y Siu
    Population Council, Center for Biomedical Research, New York, New York 10021, USA
    Biol Reprod 70:945-64. 2004
    ..It was postulated that proteases and protease inhibitors worked in a yin-yang relationship to regulate these events...
  65. pmc Malaria parasite exit from the host erythrocyte: a two-step process requiring extraerythrocytic proteolysis
    B L Salmon
    Howard Hughes Medical Institute, Departments of Molecular Medicine and Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 98:271-6. 2001
    ..We propose a model for the process of rupture: merozoites enclosed within the PVM first exit from the host erythrocyte and then rapidly escape from the PVM by a proteolysis-dependent mechanism...
  66. ncbi Identification and analysis of fitness of resistance mutations against the HCV protease inhibitor SCH 503034
    Xiao Tong
    Department of Virology, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilwoth, NJ 07033, USA
    Antiviral Res 70:28-38. 2006
    ..M., Perni, R.B., Gates, C.A., Kwong, A.D., 2004. In vitro resistance studies of hepatitis C virus serine protease inhibitors, VX-950 and BILN 2061: structural analysis indicates different resistance mechanisms. J. Biol. Chem...
  67. doi Recombinant protease inhibitors for herbivore pest control: a multitrophic perspective
    Urte Schlüter
    Plant Science Department, Forestry and Agricultural Biotechnology Institute, University of Pretoria, Pretoria, South Africa
    J Exp Bot 61:4169-83. 2010
    b>Protease inhibitors are a promising complement to Bt toxins for the development of insect-resistant transgenic crops, but their limited specificity against proteolytic enzymes and the ubiquity of protease-dependent processes in living ..
  68. ncbi Distinct expression pattern of two related human proteins containing multiple types of protease-inhibitory modules
    Maria Trexler
    Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest
    Biol Chem 383:223-8. 2002
  69. pmc Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells
    Andrew Fribley
    Laboratory of Molecular Signaling and Apoptosis, Department of Biologic and Materials Sciences, University of Michigan, 1011 N University Ave, Ann Arbor, MI 48109 1078, USA
    Mol Cell Biol 24:9695-704. 2004
  70. pmc Reuse of nevirapine in exposed HIV-infected children after protease inhibitor-based viral suppression: a randomized controlled trial
    Ashraf Coovadia
    Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa
    JAMA 304:1082-90. 2010
    ..However, there are limitations of continuing PI-based therapy indefinitely and reuse of nevirapine has many advantages...
  71. pmc Vinyl sulfones as antiparasitic agents and a structural basis for drug design
    Iain D Kerr
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158 2550, USA
    J Biol Chem 284:25697-703. 2009
    ..and the first reported structure of rhodesain, in complex with a class of potent, small molecule, cysteine protease inhibitors, the vinyl sulfones...
  72. pmc Inhibition of matrix metalloproteinase-2 enhances radiosensitivity by abrogating radiation-induced FoxM1-mediated G2/M arrest in A549 lung cancer cells
    Chandramu Chetty
    Program of Cancer Biology, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605, USA
    Int J Cancer 124:2468-77. 2009
  73. pmc Structure-based discovery of dengue virus protease inhibitors
    Suzanne M Tomlinson
    Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, 77555, United States
    Antiviral Res 82:110-4. 2009
    ..The goal of this study was to identify novel dengue virus (type 2; DEN2V) protease inhibitors for eventual development as effective anti-flaviviral drugs...
  74. ncbi Matrix metalloproteinase-2 (MMP-2) regulates astrocyte motility in connection with the actin cytoskeleton and integrins
    Crystel Ogier
    Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, CNRS UMR 6184 Université de la Méditerranée, Faculte de Medecine de Marseille, IFR Jean Roche, Pierre Dramard 13916, Marseille Cedex 20, France
    Glia 54:272-84. 2006
  75. ncbi Role for matrix metalloproteinase 9 after focal cerebral ischemia: effects of gene knockout and enzyme inhibition with BB-94
    M Asahi
    Department of Neurology, Massachusetts General Hospital, and Harvard Medical School, Charlestown 02129, USA
    J Cereb Blood Flow Metab 20:1681-9. 2000
    ..These data demonstrate that MMP-9 plays a deleterious role in the development of brain injury after focal ischemia...
  76. pmc Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma
    Deborah J Kuhn
    Lineberger Comprehensive Cancer Center and Department of Medicine, Division of Hematology Oncology, University of North Carolina, Chapel Hill, NC, USA
    Blood 110:3281-90. 2007
    ..Carfilzomib also overcame resistance to other conventional agents and acted synergistically with dexamethasone to enhance cell death. Taken together, these data provide a rationale for the clinical evaluation of carfilzomib in MM...
  77. ncbi Neuroprotection by inhibition of matrix metalloproteinases in a mouse model of intracerebral haemorrhage
    Jian Wang
    Department of Pharmacological Sciences, University Medical Center at Stony Brook, Stony Brook, NY 11794 8651, USA
    Brain 128:1622-33. 2005
    ..Blockade of MMP activity during this critical period may have efficacy as a therapeutic strategy for the treatment of acute brain injury after ICH...
  78. ncbi Proteasome inhibitor, bortezomib, potently inhibits the growth of adult T-cell leukemia cells both in vivo and in vitro
    Y Satou
    Institute for Virus Research, Kyoto University, Kyoto, Japan
    Leukemia 18:1357-63. 2004
    ..These studies revealed that bortezomib is highly effective against ATL cells in vitro and in vivo by induction of apoptosis, and its clinical application might improve the prognosis of patients with this fatal disease...
  79. ncbi Relative abundance and inhibitory distribution of protease inhibitors in potato juice from cv. Elkana
    L Pouvreau
    Centre for Protein Technology, TNO-WU, P.O. Box 8129, 6700 EV Wageningen, The Netherlands
    J Agric Food Chem 49:2864-74. 2001
    b>Protease inhibitors from potato juice of cv. Elkana were purified and quantified. The protease inhibitors represent ca. 50% of the total soluble proteins in potato juice...
  80. doi A phase 2a trial of 12-week interferon-free therapy with two direct-acting antivirals (ABT-450/r, ABT-072) and ribavirin in IL28B C/C patients with chronic hepatitis C genotype 1
    Eric Lawitz
    The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, United States
    J Hepatol 59:18-23. 2013
  81. doi Fisetin and rutin as 3C protease inhibitors of enterovirus A71
    Ying Ju Lin
    Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
    J Virol Methods 182:93-8. 2012
    ..Therapeutic indices (CC50/IC50 of plaque reduction assays) of fisetin and rutin exceeded 10. The study suggests that fisetin and rutin inhibit the replication of EV-A71...
  82. doi In vivo inhibition of Helicoverpa armigera gut pro-proteinase activation by non-host plant protease inhibitors
    Vinod D Parde
    International Crops Research Institute for the Semi Arid Tropics, Patancheru, India
    J Insect Physiol 56:1315-24. 2010
    We evaluated 22 different host and non-host plant protease inhibitors (PIs) for in vivo inhibition of Helicoverpa armigera gut pro- and proteinases, and their biological activity against the pod borer, H...
  83. ncbi Eotaxin is specifically cleaved by hookworm metalloproteases preventing its action in vitro and in vivo
    F J Culley
    Leukocyte Biology Section, Biomedical Sciences Division, Imperial College School of Medicine, South Kensington, London, United Kingdom
    J Immunol 165:6447-53. 2000 response to eotaxin, but not leukotriene B(4), a phenomenon that could be prevented by the addition of protease inhibitors. Using Western blotting, N...
  84. ncbi Efficacy of continuous regional arterial infusion of a protease inhibitor and antibiotic for severe acute pancreatitis in patients admitted to an intensive care unit
    Hiroshi Imaizumi
    Department of Gastroenterology, Emergency and Critical Care Medicine, Kitasato University Hospital, Kanagawa, Japan
    Pancreas 28:369-73. 2004
    ..and the antibiotic imipenem by continuous regional arterial infusion (CRAI group) and the other received protease inhibitors and antibiotics by intravenous infusion (non-CRAI group)...
  85. pmc Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands
    Umut Sahin
    Cell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, Box 368, 1275 York Avenue, New York, NY 10021, USA
    J Cell Biol 164:769-79. 2004
    ..Identification of EGFR ligand sheddases is a crucial step toward understanding the mechanism underlying ectodomain release, and has implications for designing novel inhibitors of EGFR-dependent tumors...
  86. ncbi Unexpected cardiotoxicity in haematological bortezomib treated patients
    Orciuolo Enrico
    Br J Haematol 138:396-7. 2007
  87. ncbi Disease modifying therapy for AD?
    Todd E Golde
    Mayo Clinic College of Medicine, Department of Neuroscience, Mayo Clinic Jacksonville 4500 San Pablo Road, Jacksonville, Florida 32224, USA
    J Neurochem 99:689-707. 2006
    ..This review will highlight both the promise of and the obstacles to developing such disease modifying AD therapies...
  88. ncbi Enzymatic action of human glandular kallikrein 2 (hK2). Substrate specificity and regulation by Zn2+ and extracellular protease inhibitors
    J Lovgren
    Department of Laboratory Medicine, Lund University, Malmo, Sweden
    Eur J Biochem 262:781-9. 1999
    ..We studied the substrate specificity of hK2 and regulation of its activity by zinc and extracellular protease inhibitors present in the prostate and seminal plasma...
  89. doi Preventing unintended proteolysis in plant protein biofactories
    Meriem Benchabane
    Departement de Phytologie, CRH INAF, Universite Laval, QC, Canada
    Plant Biotechnol J 6:633-48. 2008
    ..organ-specific transgene expression, organelle-specific protein targeting, the grafting of stabilizing protein domains to labile proteins, protein secretion in natural fluids and the co-expression of companion protease inhibitors.
  90. ncbi Proteasome inhibition and its clinical prospects in the treatment of hematologic and solid malignancies
    Heinz Ludwig
    First Department of Medicine and Medical Oncology, Wilhelminenspital, Vienna, Austria
    Cancer 104:1794-807. 2005
    ..Further studies with bortezomib as monotherapy and in combination regimens in the treatment of solid and hematologic malignancies are warranted...
  91. pmc HCV genotypes are differently prone to the development of resistance to linear and macrocyclic protease inhibitors
    Valeria Cento
    Department of Experimental Medicine and Biochemical Sciences, University of Tor Vergata, Rome, Italy
    PLoS ONE 7:e39652. 2012
    ..Because of the extreme genetic variability of hepatitis C virus (HCV), we analyzed whether specific HCV-genotypes are differently prone to develop resistance to linear and macrocyclic protease-inhibitors (PIs)...
  92. pmc Naturally occurring mutations to HCV protease inhibitors in treatment-naïve patients
    Stefania Paolucci
    Molecular Virology Unit, Virology and Microbiology Department, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy
    Virol J 9:245. 2012
    b>Protease inhibitors (PIs) to treat hepatitis C (HCV) virus infection have been approved and others are under development.
  93. pmc MDL28170, a calpain inhibitor, affects Trypanosoma cruzi metacyclogenesis, ultrastructure and attachment to Rhodnius prolixus midgut
    Vítor Ennes-Vidal
    Laboratório de Biologia Molecular e Doenças Endêmicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz FIOCRUZ, Rio de Janeiro, Brazil
    PLoS ONE 6:e18371. 2011
    ..Peptidases are relevant for crucial steps of T. cruzi life cycle; as such, it is conceivable that they may participate in the metacyclogenesis and interaction with the invertebrate host...
  94. ncbi Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma
    Owen A O'Connor
    Department of Medicine, Lymphoma and Developmental Chemotherapy Services, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    J Clin Oncol 23:676-84. 2005
    ..To determine the antitumor activity of the novel proteasome inhibitor bortezomib in patients with indolent and mantle-cell lymphoma (MCL)...
  95. ncbi The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status
    Patricia Perez-Galan
    Hematopathology Unit, Hospital Clinic, Institut d Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Spain
    Blood 107:257-64. 2006
    ..These findings should be useful to extend the therapeutic strategies in MCL patients and to improve their prognosis...
  96. ncbi Irreversible inhibitors of serine, cysteine, and threonine proteases
    James C Powers
    School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332 0400, USA
    Chem Rev 102:4639-750. 2002
  97. ncbi Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A resolution
    J Lowe
    Max Planck Institut fur Biochemie, Abteilung für Strukturforschung, Martinsried, Germany
    Science 268:533-9. 1995
    ..The binding of a peptide aldehyde inhibitor marks the active site in the central cavity at the amino termini of the beta subunits and suggests a novel proteolytic mechanism...
  98. pmc Brain distribution and elimination of recombinant human TIMP-1 after cerebral ischemia and reperfusion in rats
    Yalian Sa
    Department of Neurology, College of Medicine, University of Cincinnati, OH 45267 0532, USA
    Neurol Res 33:433-8. 2011
    ..To investigate recombinant human TIMP-1 ((125)I-rhTIMP-1) half-life in blood and its distribution in rat brain tissue after cerebral ischemia/reperfusion as part of a therapeutic development paradigm...
  99. doi Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial
    Paul Y Kwo
    Department of Medicine, Division of Gastroenterology Hepatology, Indiana University School of Medicine, Indianapolis, IN 46202 5121, USA
    Lancet 376:705-16. 2010
    ..We tested the efficacy of boceprevir, an NS3 hepatitis C virus oral protease inhibitor, when added to peginterferon alfa-2b and ribavirin...
  100. pmc Protease inhibitor-resistant hepatitis C virus mutants with reduced fitness from impaired production of infectious virus
    Tetsuro Shimakami
    Division of Infectious Diseases, Department of Medicine, Inflammatory Diseases Institute, and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
    Gastroenterology 140:667-75. 2011
    ..However, the selection of drug-resistant mutants is a significant issue with protease inhibitors (PIs). A variety of amino acid substitutions in the protease domain of NS3 can lead to PI resistance...
  101. pmc Correction of the mineralization defect in hyp mice treated with protease inhibitors CA074 and pepstatin
    Peter S N Rowe
    Department of Internal Medicine, The Kidney Institute and Division of Nephrology, MS 3018, University of Kansas Medical Center, 3901 Rainbow Boulevard, 6020B Wahl Hall East, Kansas City, KS 66160, USA
    Bone 39:773-86. 2006
    ..Serum FGF23 levels remained high in all hyp animal groups (P < 0.0001). Hyp mice treated with protease inhibitors showed dramatic reductions in unmineralized osteoid (femurs) compared to control hyp mice (Goldner staining)..

Research Grants70

  1. Mice Humanized with Hepatocytes and iPS Cells from Patients with Metabolic Diseas
    Stephen C Strom; Fiscal Year: 2010
    ..We propose these humanized mice will be a technology platform to better understand the human disease and it will aid in the development of gene or cellular therapy to correct these devastating diseases. ..
  2. Serpin Modulation of Inflammatory Vasculitis; Potential for Immunomodulatory Ther
    ALEXANDRA ROSE LUCAS; Fiscal Year: 2010
    ..We have successfully tested one of these serpins, Serp-1, in a small phase 2A clinical trial for anti-inflammatory activity in unstable coronary syndromes (Viron Therapeutics, Inc;proprietary information). ..
  3. Tissue-specific delivery of probes by control of membrane trafficking of endoprot
    Blake Peterson; Fiscal Year: 2010
    ..elegans. Optimized peptide substrates will be converted into protease inhibitors by modification with C-terminal aldehyde and/or other protease inhibitory motifs at putative sites of ..
  4. Drug Interactions at the Human Blood-Brain Barrier
    Jashvant D Unadkat; Fiscal Year: 2010
    ..g. anti-HIV protease inhibitors)...
  5. Effect of HIV protease inhibitor on alcohol induced ER stress and liver injury.
    Cheng Ji; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): HIV protease inhibitors (HIV PIs) are used in the highly ctive antiretroviral therapy (HAART). However, HIV PIs are often associated with development of liver damages...
  6. The biology of blood-testis barrier dynamics
    C Yan Cheng; Fiscal Year: 2013
    ..TNF? regulates BTB dynamics via its effects on basement membrane proteins, such as collagens, proteases and protease inhibitors, which, in turn, regulates the steady-state levels of integral membrane proteins at the BTB...
  7. Amoeboid Membrane Dynamics in Prostate Cancer
    Michael R Freeman; Fiscal Year: 2013
    ..phenotypic shift that can affect migration of tumor cells through matrices and reduce their sensitivity to protease inhibitors. DRF3 also inhibits the secretion of bioactive microvesicles capable of altering the tumor microenvironment ..
  8. Cell death regulation in proteotoxic therapy
    Wei Xing Zong; Fiscal Year: 2013
    ..At the clinical level, it may establish LC3 or SCCA1 as a molecular signature for suggesting treatment with proteotoxic agents. ..
  9. Alcohol &Antiretrovirals in HIV Infection, Oxidative Stress and Liver Disease
    Marianna K Baum; Fiscal Year: 2012
    ..Nucleoside reverse transcriptase inhibitors (NRTI) in combination with non-NRTIs and protease inhibitors have demonstrated their effectiveness as antiretroviral drugs against HIV-1 despite their well-described ..
  10. High-throughput multiplex microsphere screening for toxin protease inhibitors
    Steven W Graves; Fiscal Year: 2012
    ..In this way, this proposal will discover important new compounds that can be the basis of new pharmaceuticals to treat Botulinum neurotoxin poisoning or late stage Anthrax infections. ..
  11. Drug Transport at the Blood-Testis Barrier
    Nathan J Cherrington; Fiscal Year: 2013
    ..Indeed, protease inhibitors and non-nucleoside reverse transcriptase inhibitors are actively excluded at the BTB and do not reach ..
  12. Regulation of NETosis in antibacterial lung defense
    EILEEN REMOLD-O'DONNELL; Fiscal Year: 2013
    ..We will determine whether the require NSP is located on the cell surface by the use of non-permeable serine protease inhibitors. The second aim builds on our recent findings that SerpinB1 migrates into the nucleus early during NETosis ..
  13. Development of Transdermal Films for the the Delivery of HIV Therapeutics
    Anthony Sang Won Ham; Fiscal Year: 2010
    ..relevant drug resistant virus strains and against multi-drug resistant virus strains with resistance to protease inhibitors. Due to low solubility and poor penetration through the mucosa to the target site of action, ..
  14. Cytoskeletal Keratins in Epithelial Immunity to Bacterial Keratitis
    K P CONNIE TAM; Fiscal Year: 2013
    ..Proteasome and protease inhibitors coupled with FPLC will be used to identify the proteases that generate KDAMPs...
  15. Dietary Regulation of Pancreatic Digestive Enzymes
    John A Williams; Fiscal Year: 2013
    ..Knowledge from this project should allow designing approaches to assist the human pancreas to regenerate and ensure an adequate supply of pancreatic digestive enzymes. ..
  16. NAPS2 Continuation Genome Wide Association Study of Pancreatitis
    DAVID CLEMENT WHITCOMB; Fiscal Year: 2011
    ..abstract_text> ..
  17. A New Pathway for Neutrophil-induced Airway Inflammation
    J Edwin Blalock; Fiscal Year: 2013
    ..If successful, the current proposal will yield fundamental insights into the disease process and a new and specific biomarker for COPD as well as suggesting new therapeutic targets. ..
  18. Control of HIV drug resistance in older patients
    Alonso Heredia; Fiscal Year: 2010
    ..Importantly, CCR5 antagonists, unlike HIV non-nucleoside reverse transcriptase and protease inhibitors, neither induce nor inhibit cytochrome P450 3A4, which is responsible for the metabolism of many ..
  19. Tick feeding regulation by orthologous tick saliva serine protease inhibitors
    Albert Mulenga; Fiscal Year: 2013
    ..characterization and validation of Amblyomma americanum and Ixodes scapularis tick saliva serine protease inhibitors (serpins) as vaccine target antigens for immunization of white tailed deer against tick infestation...
  20. K777 for treatment of Chagas Disease: IND-enabling Studies and IND Submission
    Robert Don; Fiscal Year: 2012
    ..novel chemical entity originally identified at University of California San Francisco by screening cysteine protease inhibitors against T. cruzi infected macrophages and evaluating growth inhibition of intracellular amastigotes...
  21. Role of Oxidative Stress and Inflammation in HIV Cardiovascular Risk
    Cecilia M Shikuma; Fiscal Year: 2012
    ..While dyslipidemia and insulin resistance induced by protease inhibitors and other classes of HIV medications likely contribute to this increased risk, there is now substantial ..
  22. Novel Protective Antiapoptotic Action of Alpha 1-Antitrypsin In Emphysema
    Rubin M Tuder; Fiscal Year: 2011
    ..with alpha-1 antitrypsin (A1AT) deficiency emphasizes the role of A1AT as an elastase inhibitor, serine protease inhibitors (Serpins), including A1 AT, have broader biological effects beyond their classical action as protease ..
  23. Plasminogen activator inhibitor-1 in tumor progression and metastasis
    Yves A DeClerck; Fiscal Year: 2013 applicant): Plasminogen activator inhibitor-1 (PAI-1) is a member of the family of endogenous serine protease inhibitors (serpins) that controls the activation of plasminogen into plasmin by tissue and urokinase type plasminogen ..
  24. Anti HCV Protease Activities of Metalloporphyrins
    Warren N Schmidt; Fiscal Year: 2013
    ..Although the first generation of HCV protease inhibitors is a noticeable step forward, it is imperative that we continue to pursue new, more effective antivirals ..
  25. The function(s) of serpin-2 in mosquito immunity and physiology
    Kristin Michel; Fiscal Year: 2013
    ..Therefore, the proposed project is relevant to the NIH-NIAID's mission in relation to the understanding and prevention of re-emerging infectious diseases. ..
  26. Syndecan-1 in Aortic Aneurysm Formation
    Elliot Chaikof; Fiscal Year: 2012 performed to define the ability of syndecan-1 to bind and inhibit selected chemokines, proteases, or protease inhibitors. (4) Determine the effectiveness of multivalent heparanoid glycodendrimers, as a syndecan-mimetic, in ..
    Nigel W Bunnett; Fiscal Year: 2010
    ..Aim 1 uses PAR2 deficient mice and protease inhibitors to determine the contribution of PAR2 and endogenous proteases to inflammation and pain...
  28. Role of Fibrinolytic System in Vein Graft Remodeling
    William P Fay; Fiscal Year: 2013
    ..We anticipate that the information gained from our experiments will lead to new strategies to treat and prevent vein graft disease. ..
  29. Antimalarial Pharmacology in HIV Coinfected Children and Pregnant Women in Uganda
    Sunil Parikh; Fiscal Year: 2013
    ..Findings should lead to specific artemether-lumefantrine dosing guidelines based on age, pregnancy, and use with concomitant antiretroviral therapy in HIV-infected populations. ..
    Mark R Denison; Fiscal Year: 2013
    ..Rational design of protease inhibitors has targeted conserved structure/function elements such as active-site cavities and substrate-binding ..
  31. Exploiting Protease-Activatable Agents to Characterize and Treat Asthma
    Csilla Felsen; Fiscal Year: 2013
    ..We propose to increase the efficacy of asthma therapeutic agents by attaching ACPPs to glucocorticoids and protease inhibitors, such as dexamethasone and marimastat, respectively, and administering them intravenously or intranasally ..
  32. Multiplex ALEX-based Test for Protease Activity Profiling in Arthritic Joints
    ARMIN H REITMAIR; Fiscal Year: 2013
    ..prove highly useful for facilitating treatment (as well as clinical trials) of arthritis with suitale protease inhibitors, or combinations thereof, personalized according to an individual patient's profile...
  33. Regulation of Pal-1 in Atherosclerosis and Thrombosis
    Yolanda M Fortenberry; Fiscal Year: 2013
    ..This is particularly important, since to date, there are no PAI-1 inhibitors available for clinical use (End of Abstract) ..
  34. Virulence-Associated Proteins of Pathogenic Leptospira Species
    James Matsunaga; Fiscal Year: 2012
    ..Novel treatments for leptospirosis can also be developed by identifying protease inhibitors of the leptospiral enzyme that causes LigA to be released from the bacteria thereby possibly facilitating ..
    Radhakrishnan P Iyer; Fiscal Year: 2010
    ..SB 9200 is synergistic with other anti-HCV agents such as nucleoside analogs, interferon, protease inhibitors, and ribavirin. SB 9200 represents potentially the next generation anti-HCV therapeutic...
  36. Designing HIV Protease Inhibitors with Lower Dosing Requirements and Lower Toxici
    Mitchell W Mutz; Fiscal Year: 2013
    ..HIV protease inhibitors are a mainstay of highly active antiretroviral therapy (HAART) with annual sales of over $2.5 billion...
  37. NeuroAIDS Therapy in the EcoHIV Mouse Model
    DAVID VOLSKY; Fiscal Year: 2009
  38. Mechanisms of Impaired Wound Healing Due to Ischemia
    Lisa J Gould; Fiscal Year: 2012
    ..and Regeneration, 2005) will be used to measure oxidative stress, endogenous antioxidants, proteases, and protease inhibitors in ischemic and non-ischemic wounds of young, middle aged and old rats, comparing these factors to the ..
    Steven T Olson; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Serpin family protein protease inhibitors function as key regulators of blood coagulation proteases...
  40. Identification of novel HIV capsid assembly inhibitors (Hit-to-Lead development)
    OSVALDO ARIEL FLORES; Fiscal Year: 2011
    ..Molecules that target HIV Capsid assembly offer a unique promise of providing high genetic barrier to resistance as well as complement existing therapies as part of combination therapy. ..
  41. Role of Calpastatin in mutant SOD1-mediated motor neuron disease
    Mala V Rao; Fiscal Year: 2010
    ..We will test a protease inhibitor (Calpain-inhibitor, CAST) treatment in mouse model of ALS to prevent motor neuron disease. If we succeed with our approach, we would like to develop specific calpain inhibitor therapy for ALS. ..
  42. Female Genital Innate Immune Response to Vaginal Microbiota
    Caroline M Mitchell; Fiscal Year: 2013
    ..This will allow development of targeted preventive and therapeutic interventions to reduce the adverse clinical outcomes. ..
  43. Cardioprotective Efficacy ofMg-Supplementation during HAART Therapy
    IVAN TONG MAK; Fiscal Year: 2011
    ..Several protease inhibitors (PI), RTV in particular, and EFV can cause elevated endothelial cell reactive oxygen species generation and ..
  44. LDL Receptor Related Protein-1 in Metabolic and Cardiovascular Disease Modulation
    David Y Hui; Fiscal Year: 2013
  45. A carboxypeptidase in the regulation of hypothalamic circuitry
    Sabrina Diano; Fiscal Year: 2013
    ..Inhibition of PRCP activity by small molecule protease inhibitors administered peripherally or centrally decreased food intake in wild type as well as obese animals...
  46. Interaction of Alcohol and HAART in HIV/AIDS and HIV/AIDS and HCV Coinfection
    Elinore F McCance Katz; Fiscal Year: 2011
    ..g.: protease inhibitors;particularly ritonavir which is frequently co-administered with other protease inhibitors to delay their ..
  47. Anti-Inflammatory mechanisms of soybean-derived Bowman-Birk protease inhibitor
    Abdolmohamad Rostami; Fiscal Year: 2012
    ..We believe that these studies will provide in depth insights into anti-inflammatory actions of BBI, and facilitate its use as a supplementary treatment for inflammatory diseases. ..
  48. A novel diagnostic biomarker for hepatocellular carcinoma and cholangiocarcinoma
    Xuanyong Lu; Fiscal Year: 2012
  49. Serpin Regulation of Coagulation Proteases
    Alireza R Rezaie; Fiscal Year: 2013
    ..provided by applicant): The proteolytic activity of coagulation proteases is regulated by the serine protease inhibitors (serpins) in plasma...
    Alan S Perelson; Fiscal Year: 2012 focus on modeling new treatments with specifically targeted anti-HCV agents, such as HCV polymerase and protease inhibitors. With these new agents the development of resistance is a great concern and we will expand models of viral ..
    Alan S Perelson; Fiscal Year: 2011 focus on modeling new treatments with specifically targeted anti-HCV agents, such as HCV polymerase and protease inhibitors. With these new agents the development of resistance is a great concern and we will expand models of viral ..
    Michael R Kanost; Fiscal Year: 2013
    ..and transcriptome sequence data to identify and annotate genes encoding putative serine proteases and protease inhibitors and to produce reagents for further experimentation. 2...
  53. Modeling viral entry and its inhibition using SARS-CoV
    Graham Simmons; Fiscal Year: 2012
    ..We base these hypotheses on the observations that: (1) broad spectrum and specific protease inhibitors able to block cathepsin L efficiently inhibit SARS-CoV entry;(2) recombinant cathepsin L, as well as a ..
    Robert P Schleimer; Fiscal Year: 2013
    ..Our successful completion of the aims described in this proposal will yield valuable new insight into the mechanisms of glucocorticoid action in human disease. ..
  55. Exploration of novel pan-HPV treatments to block development of AIDS-associated c
    Wijbe Martin Kast; Fiscal Year: 2010
  56. Regulation of IL-10 Gene Expression and Host Septic Response by Progranulin
    Xiaojing Ma; Fiscal Year: 2011
    ..abstract_text> ..
  57. Patient self-management and gene guided therapy for CHC
    Donald E Bailey; Fiscal Year: 2013
    ..a new blood test for a genetic polymorphism near the interleukin 28B (IL28B) gene and two newly approved protease inhibitors are used to enhance patient response...
  58. Moving Towards More Individualized Therapies in HIV/HCV Co-infected Patients
    Susanna Naggie; Fiscal Year: 2013
    ..With improved SVR rates, but more expensive combination regimens, the ability to individualize treatment decisions regarding the utility and benefit of HCV therapy will be critical. ..
  59. Mechanisms of Deregulation of Matriptase in Breast Cancer
    Chen Yong Lin; Fiscal Year: 2013
  60. Preparing for New Antivirals: Preferences for Treatment of Hepatitis C
    Liana Fraenkel; Fiscal Year: 2013
  61. Enhancing Intestinal &Brain Uptake of Anti-AIDS Drugs
    Patrick J Sinko; Fiscal Year: 2013
    ..using multiplex affinity ligands for the formyl peptide receptor, mannose receptor, CCR5 and CXCR4 using protease inhibitors in cells chronically infected with HIV-1;(2) To determine the effect of peptide-polymer scaffold topology, ..
  62. Advancing clemizole for hepatitis C: towards a pre-IND package
    Jeffrey S Glenn; Fiscal Year: 2010
    ..hypothesize that: 1) clemizole's dramatic synergy with SCH503034 extends to the general class of HCV protease inhibitors, and possibly other agents;2) clemizole-resistant mutants will retain their sensitivity to protease ..
  63. Cellular Efflux and Metabolism of Protease Inhibitors
    Ashim Mitra; Fiscal Year: 2004
    ..P-glycoprotein (P-gp), the MDR-1 gene product is also known to reduce the oral bioavailability of protease inhibitors. Moreover the existence of "sanctuary" sites of HIV-1 may potentially endanger the efficacy of highly ..
  64. AREA: Synthesis and Evaluation of New Cathepsin B, D, and K Inhibitors
    Rose McConnell; Fiscal Year: 2009
    ..There is an urgent need for new, more effective protease inhibitors as therapeutic agents...
  65. Dengue and West Nile Viral Protease Inhibitors
    Radhakrishnan Padmanabhan; Fiscal Year: 2005
    ..Nile viral protease and characterize its biochemical and kinetic properties in the presence and absence of protease inhibitors. This objective will be achieved with the following Specific Aims...
  66. TDM & Drug Interactions in HIVinfected Substance Abusers
    Gene Morse; Fiscal Year: 2007
    ..application describes an innovative approach to the rapid assessment of complex drug interactions between protease inhibitors and nonnucleoside reverse transcriptase inhibitors (NNRTIs), and commonly prescribed medications including ..
  67. Serpin Protease Inhibitors & Opioid Neuropeptides
    Vivian Hook; Fiscal Year: 2006
    ..These observations suggest that endogenous protease inhibitors may be involved in proneuropeptide processing...
    Virgil Brown; Fiscal Year: 2004
    DESCRIPTION (Adapted from the applicant's abstract) HIV-protease inhibitors (PI) prevent the maturation of nascent virions and are thus very effective in blocking further infection in HIV-positive patients...
    Brian Liu; Fiscal Year: 1993
    The purpose of this proposal is to determine the effects of protease inhibitors in the abrogation of invasion by human bladder tumor cells...
    Changyi Chen; Fiscal Year: 2004
    DESCRIPTION (Adapted from the applicant's abstract) 1). To define the role of HIV protease inhibitors in endothelium-dependent vasorelaxation and endothelial morphology...