N Neamati

Summary

Affiliation: University of Southern California
Country: USA

Publications

  1. ncbi request reprint Novel dimeric aryldiketo containing inhibitors of HIV-1 integrase: effects of the phenyl substituent and the linker orientation
    Li Fan Zeng
    State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China
    Bioorg Med Chem 16:7777-87. 2008
  2. ncbi request reprint Synthesis and biological evaluation of novel 5(H)-phenanthridin-6-ones, 5(H)-phenanthridin-6-one diketo acid, and polycyclic aromatic diketo acid analogs as new HIV-1 integrase inhibitors
    Shivaputra Patil
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA
    Bioorg Med Chem 15:1212-28. 2007
  3. ncbi request reprint Discovery of a novel quinoxalinhydrazide with a broad-spectrum anticancer activity
    Carmen Plasencia
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90033, USA
    Cancer Biol Ther 8:458-65. 2009
  4. ncbi request reprint Small-molecule inhibitors of p53-MDM2 interaction: the 2006-2010 update
    Melissa Millard
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, PSC 304, Los Angeles, CA 90089 9121, USA
    Curr Pharm Des 17:536-59. 2011
  5. pmc Small molecule inhibitors of CXCR4
    Bikash Debnath
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, PSC 304, Los Angeles, CA 90089 9121, USA
    Theranostics 3:47-75. 2013
  6. pmc Mechanistic evaluation of a novel small molecule targeting mitochondria in pancreatic cancer cells
    Yumna H Shabaik
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA
    PLoS ONE 8:e54346. 2013
  7. pmc A symmetric region of the HIV-1 integrase dimerization interface is essential for viral replication
    Erik Serrao
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA
    PLoS ONE 7:e45177. 2012
  8. pmc Raltegravir: The evidence of its therapeutic value in HIV-1 infection
    Kavya Ramkumar
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, USA
    Core Evid 4:131-47. 2010
  9. pmc Integrin targeted therapeutics
    Melissa Millard
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, PSC304 1985 Zonal Avenue, Los Angeles, CA 90089
    Theranostics 1:154-88. 2011
  10. doi request reprint Discovery of a novel orally active small-molecule gp130 inhibitor for the treatment of ovarian cancer
    Shili Xu
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90033, USA
    Mol Cancer Ther 12:937-49. 2013

Collaborators

Detail Information

Publications85

  1. ncbi request reprint Novel dimeric aryldiketo containing inhibitors of HIV-1 integrase: effects of the phenyl substituent and the linker orientation
    Li Fan Zeng
    State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China
    Bioorg Med Chem 16:7777-87. 2008
    ..This study is a significant extension of our previous report on the dimeric ADK-containing IN inhibitors, providing a new promising template for further lead optimization...
  2. ncbi request reprint Synthesis and biological evaluation of novel 5(H)-phenanthridin-6-ones, 5(H)-phenanthridin-6-one diketo acid, and polycyclic aromatic diketo acid analogs as new HIV-1 integrase inhibitors
    Shivaputra Patil
    Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA
    Bioorg Med Chem 15:1212-28. 2007
    ....
  3. ncbi request reprint Discovery of a novel quinoxalinhydrazide with a broad-spectrum anticancer activity
    Carmen Plasencia
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90033, USA
    Cancer Biol Ther 8:458-65. 2009
    ..Considering its cytotoxicity profile in a variety of in vitro and in vivo cancer models as well as its effects on cell cycle regulation and apoptosis, SC144 appears to represent a promising agent for further clinical development...
  4. ncbi request reprint Small-molecule inhibitors of p53-MDM2 interaction: the 2006-2010 update
    Melissa Millard
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, PSC 304, Los Angeles, CA 90089 9121, USA
    Curr Pharm Des 17:536-59. 2011
    ..It remains to be seen how these inhibitors will perform in future clinical studies as single agents and in combination with the currently approved chemotherapeutic agents...
  5. pmc Small molecule inhibitors of CXCR4
    Bikash Debnath
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, PSC 304, Los Angeles, CA 90089 9121, USA
    Theranostics 3:47-75. 2013
    ....
  6. pmc Mechanistic evaluation of a novel small molecule targeting mitochondria in pancreatic cancer cells
    Yumna H Shabaik
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA
    PLoS ONE 8:e54346. 2013
    ....
  7. pmc A symmetric region of the HIV-1 integrase dimerization interface is essential for viral replication
    Erik Serrao
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA
    PLoS ONE 7:e45177. 2012
    ....
  8. pmc Raltegravir: The evidence of its therapeutic value in HIV-1 infection
    Kavya Ramkumar
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, USA
    Core Evid 4:131-47. 2010
    ....
  9. pmc Integrin targeted therapeutics
    Melissa Millard
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, PSC304 1985 Zonal Avenue, Los Angeles, CA 90089
    Theranostics 1:154-88. 2011
    ..Herein, this review examines and evaluates the various drugs and compounds targeting integrins and the disease states in which they are implicated...
  10. doi request reprint Discovery of a novel orally active small-molecule gp130 inhibitor for the treatment of ovarian cancer
    Shili Xu
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90033, USA
    Mol Cancer Ther 12:937-49. 2013
    ..In addition, SC144 shows potent inhibition of gp130 ligand-triggered signaling. Oral administration of SC144 delays tumor growth in a mouse xenograft model of human ovarian cancer without significant toxicity to normal tissues...
  11. ncbi request reprint Small-molecule inhibitors of APE1 DNA repair function: an overview
    Rasha I Al-Safi
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90089, USA
    Curr Mol Pharmacol 5:14-35. 2012
    ....
  12. pmc Raltegravir, elvitegravir, and metoogravir: the birth of "me-too" HIV-1 integrase inhibitors
    Erik Serrao
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, Los Angeles, CA 90089, USA
    Retrovirology 6:25. 2009
    ....
  13. ncbi request reprint New paradigms in drug design and discovery
    Nouri Neamati
    University of Southern California, School of Pharmacy, Department of Pharmaceutical Sciences, Los Angeles 90089 9121, USA
    Curr Top Med Chem 2:211-27. 2002
    ..In this review, we will attempt to outline these latest protocols that chemists and biomedical scientist are currently employing to rapidly bring new drugs to the clinic...
  14. ncbi request reprint Dipyrimidine-based inhibitors of HIV-1 integrase
    Nouri Neamati
    Department of Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, USA
    Expert Opin Investig Drugs 12:289-92. 2003
  15. ncbi request reprint Structure-based HIV-1 integrase inhibitor design: a future perspective
    N Neamati
    University of Southern California, School of Pharmacy, 1985 Zonal Avenue, PSC 304BA, Los Angeles, CA 90089 9121, USA
    Expert Opin Investig Drugs 10:281-96. 2001
    ..However, because of recent developments in the field such information could soon become available. In this review, emphasis is placed on inhibitors with identified or proposed drug binding sites on IN...
  16. ncbi request reprint Metal-dependent inhibition of HIV-1 integrase
    Nouri Neamati
    Department of Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, California 90089, USA
    J Med Chem 45:5661-70. 2002
    ..These data suggest that MSHs are selective inhibitors of HIV-1 IN and may serve as leads for antiviral therapeutics...
  17. ncbi request reprint Small-molecule HIV-1 integrase inhibitors: the 2001-2002 update
    Raveendra Dayam
    Department of Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, PSC 304A, Los Angeles, CA 90089 9121, USA
    Curr Pharm Des 9:1789-802. 2003
    ..However, based on the growing body of literature certain classes of compounds can be easily excluded as bona fide IN inhibitors...
  18. ncbi request reprint Mining the NCI antiviral compounds for HIV-1 integrase inhibitors
    Jinxia Deng
    Department of Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90089, USA
    Bioorg Med Chem 14:3785-92. 2006
    ..The tested inhibitors exhibit favorable interactions with important amino acid residues through van der Waals and H-bonding contacts...
  19. ncbi request reprint Active site binding modes of the beta-diketoacids: a multi-active site approach in HIV-1 integrase inhibitor design
    Raveendra Dayam
    Department of Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, PSC 304, Los Angeles, CA 90089, USA
    Bioorg Med Chem 12:6371-81. 2004
    ..Therefore, we propose that this active site conformation is the biologically relevant conformation and can be used for the future structure-based drug design studies selectively targeting IN...
  20. ncbi request reprint Beta-diketo acid pharmacophore hypothesis. 1. Discovery of a novel class of HIV-1 integrase inhibitors
    Raveendra Dayam
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, California 90089, USA
    J Med Chem 48:111-20. 2005
    ..This is the first reported use of S-1360 and its analogues as leads in developing a pharmacophore hypothesis for IN inhibition and for identification of new compounds with potent inhibition of this enzyme...
  21. doi request reprint Quinolone 3-carboxylic acid pharmacophore: design of second generation HIV-1 integrase inhibitors
    Raveendra Dayam
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, California 90089, USA
    J Med Chem 51:1136-44. 2008
    ....
  22. ncbi request reprint Anti-infectives: clinical progress of HIV-1 integrase inhibitors
    Laith Q Al-Mawsawi
    University of Southern California, Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, Los Angeles, California 90089, USA
    Expert Opin Emerg Drugs 13:213-25. 2008
    ....
  23. ncbi request reprint Substituted 2-pyrrolinone inhibitors of HIV-1 integrase
    Raveendra Dayam
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA
    Bioorg Med Chem Lett 17:6155-9. 2007
    ..J. Med. Chem.2005, 48, 8009]. In efforts to optimize this class of IN inhibitors, we carried out a structure-activity relationship analysis around the 2-pyrrolinone core. Here, we present a new class of 2-pyrrolinone IN inhibitors...
  24. pmc Discovery of a small-molecule HIV-1 integrase inhibitor-binding site
    Laith Q Al-Mawsawi
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA
    Proc Natl Acad Sci U S A 103:10080-5. 2006
    ..This type of structural information can help illuminate processes of inhibitor resistance and thereby facilitate the design of more potent second-generation inhibitors...
  25. doi request reprint Pharmacophore guided discovery of small-molecule human apurinic/apyrimidinic endonuclease 1 inhibitors
    Zahrah Zawahir
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90033, USA
    J Med Chem 52:20-32. 2009
    ..All of our most potent molecules show inhibitory activity below 10 muM and are selective for APE1 inhibition...
  26. ncbi request reprint Discovery of 3-acetyl-4-hydroxy-2-pyranone derivatives and their difluoridoborate complexes as a novel class of HIV-1 integrase inhibitors
    Kavya Ramkumar
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, Room 304, 1985 Zonal Avenue, Los Angeles, CA 90089, USA
    Bioorg Med Chem 16:8988-98. 2008
    ..Compound 9 was most active with an IC(50) value of 9 microM and 3 microM for 3'-processing and strand transfer inhibition, respectively...
  27. ncbi request reprint Design of second generation HIV-1 integrase inhibitors
    Jinxia Deng
    Department of Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, California 90089, USA
    Curr Pharm Des 13:129-41. 2007
    ..In this article we have comprehensively reviewed the application of pharmacophore-based drug design methods in the field of IN inhibitor discovery...
  28. ncbi request reprint Discovery and structure-activity relationship studies of a unique class of HIV-1 integrase inhibitors
    Raveendra Dayam
    Department of Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, California 90089, USA
    ChemMedChem 1:238-44. 2006
    ..The predicted bound conformation of the most active analogues inside the IN active site also supports the observed structure-activity correlation in this new compound class...
  29. ncbi request reprint Single amino acid substitution in HIV-1 integrase catalytic core causes a dramatic shift in inhibitor selectivity
    Laith Q Al-Mawsawi
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA
    FEBS Lett 581:1151-6. 2007
    ..Even though IN utilizes the same active site for both reactions, this finding suggests a distinct conformational dissimilarity in the mechanistic details of each IN catalytic event...
  30. ncbi request reprint Discovery of structurally diverse HIV-1 integrase inhibitors based on a chalcone pharmacophore
    Jinxia Deng
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90089, USA
    Bioorg Med Chem 15:4985-5002. 2007
    ..The identified compounds have the potential to exhibit favorable pharmacokinetic and pharmacodynamic profiles...
  31. ncbi request reprint Application of CoMFA and CoMSIA 3D-QSAR and docking studies in optimization of mercaptobenzenesulfonamides as HIV-1 integrase inhibitors
    Chih Ling Kuo
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, PSC 304, Los Angeles, California 90089, USA
    J Med Chem 47:385-99. 2004
    ..For compounds with closely related structures, binding energies given by the FlexX scoring function correlated with HIV-1 IN inhibitory activity...
  32. ncbi request reprint Blocking interactions between HIV-1 integrase and cellular cofactors: an emerging anti-retroviral strategy
    Laith Q Al-Mawsawi
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90089, USA
    Trends Pharmacol Sci 28:526-35. 2007
    ..Our discussion includes the identified IN cellular cofactors, key research developments in the field and the implications this approach will have on the current HIV treatment regimen...
  33. ncbi request reprint HIV-1 integrase inhibitors: an emerging clinical reality
    Raveendra Dayam
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90089, USA
    Drugs R D 8:155-68. 2007
    ..These agents include S-1360, GSK-364735, L-870,810, L-870,812, MK-0518, GS-9137, L-900564, GS-9224, and BMS-707035. Promising antiviral activity has already been achieved with MK-0518 and GS-9137 in late-stage clinical studies...
  34. ncbi request reprint HIV-1 integrase inhibitors: 2005-2006 update
    Raveendra Dayam
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, Los Angeles, California 90089, USA
    Med Res Rev 28:118-54. 2008
    ..Continued efforts in the field have resulted in the discovery of compounds from diverse chemical classes. In this review, we provide a comprehensive report of all IN inhibitors discovered in the years 2005 and 2006...
  35. ncbi request reprint Diketo acid pharmacophore. 2. Discovery of structurally diverse inhibitors of HIV-1 integrase
    Raveendra Dayam
    Department of Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, PSC304, Los Angeles, California 90089, USA
    J Med Chem 48:8009-15. 2005
    ..Out of the 27 compounds, 13 compounds inhibited strand transfer activity of IN with an IC50 value less than 30 microM. These compounds are novel, druglike, and readily amenable for synthetic optimization...
  36. ncbi request reprint Discovery of novel non-cytotoxic salicylhydrazide containing HIV-1 integrase inhibitors
    Laith Q Al-Mawsawi
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA
    Bioorg Med Chem Lett 17:6472-5. 2007
    ..The novel hydrazides displayed low micromolar IN inhibitory activity and are several hundred-fold less cytotoxic than previously disclosed salicylhydrazide IN inhibitors...
  37. doi request reprint Discovery of novel small-molecule inhibitors of human epidermal growth factor receptor-2: combined ligand and target-based approach
    Rambabu Gundla
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA, USA
    J Med Chem 51:3367-77. 2008
    ..Seven compounds inhibited growth of SKBR3 cells with IC50 values <10 microM. These lead compounds have desirable physicochemical properties and are excellent candidates for further optimization...
  38. ncbi request reprint Inhibition of HIV-1 integrase activity by synthetic peptides derived from the HIV-1 HXB2 Pol region of the viral genome
    Zahrah Zawahir
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, 90089, USA
    Bioorg Med Chem Lett 16:5199-202. 2006
    ..These peptides, and their analogs, may potentially be used in the elucidation of structural and functional epitopes of IN involved in protein-protein and protein-small molecule interactions...
  39. doi request reprint Inhibitory profile of a LEDGF/p75 peptide against HIV-1 integrase: insight into integrase-DNA complex formation and catalysis
    Laith Q Al-Mawsawi
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA
    FEBS Lett 582:1425-30. 2008
    ..These results shed light on IN-DNA multimeric formation, and how this process influences the LEDGF/p75-IN interaction...
  40. ncbi request reprint Structure-based inhibitor design targeting HIV-1 integrase
    I Jen Chen
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 20 N Pine Street, Baltimore, MD 21201, USA
    Curr Drug Targets Infect Disord 2:217-34. 2002
    ..Structure-based drug design efforts are then critiqued, including both ligand-based (e.g. pharmacophore) and target-based (e.g. docking) methods. Results from recent computational chemistry studies of IN are also discussed...
  41. ncbi request reprint Small molecules anti-HIV therapeutics targeting CXCR4
    Fedora Grande
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089, USA
    Curr Pharm Des 14:385-404. 2008
    ..We aim to provide a comprehensive summary of diverse structural templates that could be useful for optimization and discovery of novel CXCR4 antagonists...
  42. doi request reprint Discovery of novel anticancer compounds based on a quinoxalinehydrazine pharmacophore
    Jinxia Deng
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, California 90089, USA
    ChemMedChem 3:1677-86. 2008
    ....
  43. ncbi request reprint Expression analysis of genes involved in oxaliplatin response and development of oxaliplatin-resistant HT29 colon cancer cells
    C Plasencia
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, 90033, USA
    Int J Oncol 29:225-35. 2006
    ..This study provides the basis for further evaluation of these putative markers of OXA response and resistance in colorectal cancer patients who are candidates for treatment with OXA...
  44. ncbi request reprint Four-tiered pi interaction at the dimeric interface of HIV-1 integrase critical for DNA integration and viral infectivity
    Laith Q Al-Mawsawi
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA
    Virology 377:355-63. 2008
    ..The rational design of small molecule inhibitors targeting the disruption of this pi-pi interaction should lead to powerful anti-retroviral drugs...
  45. ncbi request reprint Synthesis and biological evaluation of novel hydrazide based cytotoxic agents
    Fedora Grande
    University of Southern California, School of Pharmacy, Department of Pharmacology and Pharmaceutical Sciences, Los Angeles, CA 90033, USA
    Expert Opin Investig Drugs 18:555-68. 2009
    ..Considering their cytotoxicity profiles in a variety of in vitro and in vivo cancer models, these hydrazide based compounds seem to have considerable potentials as novel chemotherapeutics...
  46. ncbi request reprint Design, synthesis and structure-activity studies of rhodanine derivatives as HIV-1 integrase inhibitors
    Kavya Ramkumar
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, PSC 304, Los Angeles, CA 90033, USA
    Molecules 15:3958-92. 2010
    ..Two compounds showed significant cytotoxicity in a panel of human cancer cell lines. Taken together, our results show that rhodanines are a promising class of compounds for developing drugs with antiviral and anticancer properties...
  47. ncbi request reprint Discovery of small molecule integrin alphavbeta3 antagonists as novel anticancer agents
    Raveendra Dayam
    Department of Pharmaceutical Sciences, University of Southern California, Los Angeles, California 90033, USA
    J Med Chem 49:4526-34. 2006
    ..These small-molecule compounds could be conjugated to paclitaxel for selective delivery to alphavbeta3 positive metastatic cancer cells...
  48. doi request reprint Are we living in the end of the blockbuster drug era?
    Bikash Debnath
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90089, USA
    Drug News Perspect 23:670-84. 2010
    ..A new wave of innovations is expected to boost the blockbuster regime. Herein, we discuss the different threats facing the branded monopoly, as well as some of the hopeful expectations for the blockbuster drug...
  49. ncbi request reprint Biological evaluation of paclitaxel-peptide conjugates as a model for MMP2-targeted drug delivery
    Roppei Yamada
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, Los Angeles, CA, USA
    Cancer Biol Ther 9:192-203. 2010
    ..Together, our results indicate the potential of the tumor-targeted delivery of PTX to exploit the specific recognition of MMP2, reduce toxicity, and selectively kill tumor cells...
  50. ncbi request reprint Discovery and preclinical evaluation of a novel class of small-molecule compounds in hormone-dependent and -independent cancer cell lines
    Carmen Plasencia
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, 90089, USA
    Mol Cancer Ther 4:1105-13. 2005
    ....
  51. pmc Novel opportunities for thymidylate metabolism as a therapeutic target
    Peter M Wilson
    Department of Pathology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Room 5322, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA
    Mol Cancer Ther 7:3029-37. 2008
    ....
  52. ncbi request reprint Synthesis and biological evaluation of dimeric RGD peptide-paclitaxel conjugate as a model for integrin-targeted drug delivery
    Xiaoyuan Chen
    Department of Radiology, University of Southern California, Los Angeles, California 90033, USA
    J Med Chem 48:1098-106. 2005
    ..Our results demonstrate the potential of tumor-targeted delivery of paclitaxel based on the specific recognition of cell adhesion molecule alpha(v)beta(3) integrin to reduce toxicity and enhance selective killing of cancer cells...
  53. ncbi request reprint HIV-1 integrase inhibitors: 2003-2004 update
    Raveendra Dayam
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, 90089, USA
    Med Res Rev 26:271-309. 2006
    ..Compilation of such data will prove beneficial in developing QSAR, virtual screening, pharmacophore hypothesis generation, and validation...
  54. ncbi request reprint Elucidation of the molecular mechanisms of a salicylhydrazide class of compounds by proteomic analysis
    Xuefei Cao
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA
    Curr Cancer Drug Targets 9:189-201. 2009
    ..The signaling networks identified by this work may provide the basis for future mechanistic studies. The validation of the proposed pathways and the elucidation of the signaling cross-talk are currently under way...
  55. ncbi request reprint Preparation of DNA-protein complexes suitable for spectroscopic analysis
    Nouri Neamati
    Department of Pharmaceutical Sciences, University of Southern California, School of Pharmacy, Los Angeles, CA, USA
    Methods Mol Med 85:185-202. 2003
  56. doi request reprint Opportunities in discovery and delivery of anticancer drugs targeting mitochondria and cancer cell metabolism
    Divya Pathania
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, 90089, USA
    Adv Drug Deliv Rev 61:1250-75. 2009
    ..This review provides an overview of the potential anticancer agents that act by targeting cancer cell metabolism and mitochondria, and also brings us face to face with the emerging opportunities in cancer therapy...
  57. ncbi request reprint Rational design and synthesis of novel dimeric diketoacid-containing inhibitors of HIV-1 integrase: implication for binding to two metal ions on the active site of integrase
    Ya Qiu Long
    State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, CAS, 555 Zuchongzhi Road, Shanghai 201203, China
    J Med Chem 47:2561-73. 2004
    ..This study represents the first attempt to rationally target two divalent metal ions on the active site of IN and may have potential implications for the design of second generation diketoacid-containing class of inhibitors...
  58. ncbi request reprint Design and synthesis of novel dihydroxyindole-2-carboxylic acids as HIV-1 integrase inhibitors
    Mario Sechi
    Dipartimento Farmaco Chimico Tossicologico, Universita di Sassari, Sassari, Italy
    Antivir Chem Chemother 15:67-81. 2004
    ..Further computational docking studies were performed to determine the title compounds' mode of interaction with the IN active site. The residues K156, K159 and D64 were the most important for potency against purified IN...
  59. ncbi request reprint Synthesis, antiviral, and anti-HIV-1 integrase activities of 3-aroyl-1,1-dioxo-1,4,2-benzodithiazines
    Zdzislaw Brzozowski
    Department of Chemical Technology of Drugs, Medical University of Gdansk, Al Gen Hallera 107, 80 416 Gdansk, Poland
    Bioorg Med Chem 12:3663-72. 2004
    ..In contrast to all reported IN inhibitors benzodithiazines are essentially nontoxic. Significant antiviral potency was only observed at concentration exceedingly higher than that required to inhibit purified IN...
  60. ncbi request reprint Synthesis and anti-HIV-1 activity of a novel series of 1,4,2-benzodithiazine-dioxides
    Zdzisław Brzozowski
    Department of Chemical Technology of Drugs, Medical University of Gdansk, 80 416 Gdansk, Poland
    Bioorg Med Chem Lett 16:5298-302. 2006
    ..We successfully identified a lead compound with remarkable anti-HIV-1 activity (EC(50)=0.09microM). These compounds showed minimal cytotoxicity and are therefore suitable for antiviral development...
  61. ncbi request reprint From ligand to complexes: inhibition of human immunodeficiency virus type 1 integrase by beta-diketo acid metal complexes
    Mario Sechi
    Dipartimento Farmaco Chimico Tossicologico, Universita di Sassari, Via Muroni 23 A, 07100 Sassari, Italy
    J Med Chem 49:4248-60. 2006
    ..Therefore, the difference in activities is related to the complexes they preferentially form in solution, and these findings are important for the design of a new generation of IN inhibitors...
  62. pmc Inhibition of human immunodeficiency virus type 1 integration by diketo derivatives
    Wim Pluymers
    Rega Institute for Medical Research, K U Leuven, Minderbroedersstraat 10, Belgium
    Antimicrob Agents Chemother 46:3292-7. 2002
    ..In cell culture, addition of L-708,906 could be postponed for 7 h after infection, a moment coinciding with HIV integration. Inhibition of integration in cell culture was confirmed by quantitative Alu-PCR...
  63. ncbi request reprint Structure activity of 3-aryl-1,3-diketo-containing compounds as HIV-1 integrase inhibitors
    Godwin C G Pais
    Laboratory of Medicinal Chemistry, Laboratory of Molecular Pharmacology, and HIV Drug Resistance Program, Center for Cancer Research, National Cancer Institute NIH, 376 Boyles Street, Frederick, MD 21702 1201, USA
    J Med Chem 45:3184-94. 2002
    ..Interestingly, several analogues of L-708,906 with varied substituents on the left side aryl ring, while having good inhibitory potencies against IN in extracellular assays, are not antiviral in whole-cell systems...
  64. ncbi request reprint Structural determinants for HIV-1 integrase inhibition by beta-diketo acids
    Christophe Marchand
    Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI National Institutes of Health, Bethesda, MD 20892 4255, USA
    J Biol Chem 277:12596-603. 2002
    ..We propose that the bifunctional DKA derivative binds to both the acceptor and donor sites of HIV-1 integrase, whereas the monofunctional L-708,906 derivative binds selectively to the acceptor site...
  65. ncbi request reprint Synthesis of novel thiazolothiazepine based HIV-1 integrase inhibitors
    Francesca Aiello
    Dipartimento di Scienze Farmaceutiche, Universita della Calabria, 87036 Arcavacata di Rende CS, Italy
    Bioorg Med Chem 12:4459-66. 2004
    ..The oxygen atom of the oxazolo ring of 7 and 8 could chelate Mg(2+). These results indicate that the new analogs potentially interact with the highly conserved residues important for IN catalytic activities...
  66. ncbi request reprint Design and synthesis of novel indole beta-diketo acid derivatives as HIV-1 integrase inhibitors
    Mario Sechi
    Dipartimento Farmaco Chimico Tossicologico, Universita di Sassari, Via Muroni 23 A, 07100 Sassari, Italy
    J Med Chem 47:5298-310. 2004
    ..Using this structure as a lead for all of our computational studies, we found that the title compounds extensively interact with the essential amino acids on the active site of IN...
  67. ncbi request reprint Synthesis and antitumor activities of a series of novel quinoxalinhydrazides
    Fedora Grande
    Dipartimento di Scienze Farmaceutiche, Universita della Calabria, 87036 Arcavacata di Rende CS, Italy
    Bioorg Med Chem 15:288-94. 2007
    ..Although several of the analogues showed significant activities, modification of the heteroacyl moiety had a dramatic effect on potency...
  68. pmc HIV integrase inhibitors with nucleobase scaffolds: discovery of a highly potent anti-HIV agent
    Vasu Nair
    The Center for Drug Discovery, Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia 30602, USA
    J Med Chem 49:445-7. 2006
    ..The in vitro anti-HIV data of this inhibitor were remarkable as exemplified by its highly potent antiviral therapeutic efficacy against HIV(TEKI) and HIV-1(NL4)(-)(3) replication in PBMC (TI >4,000 and >10,000, respectively)...
  69. ncbi request reprint Dynamic pharmacophore model optimization: identification of novel HIV-1 integrase inhibitors
    Jinxia Deng
    Department of Chemical Engineering, University of Houston, Houston, Texas 77204, USA
    J Med Chem 49:1684-92. 2006
    ..Twenty-two structurally novel compounds were tested in an in vitro assay specific for IN, and two of them showed IC50 < or = 10 microM for strand transfer reaction...
  70. ncbi request reprint Synthesis, antitumor and anti-HIV activities of benzodithiazine-dioxides
    Zdziasław Brzozowski
    Department of Chemical Technology of Drugs, Medical University of Gdansk, 80 416 Gdansk, Poland
    Bioorg Med Chem 14:2985-93. 2006
    ..Interestingly, benzodithiazine-dioxide 16 showed remarkable anti-HIV-1 activity with 50% effective concentration EC50 value of 0.94 microM and no significant cytotoxicity at 200.0 microM...
  71. ncbi request reprint Synthesis and biological evaluation of geminal disulfones as HIV-1 integrase inhibitors
    D Christopher Meadows
    Department of Chemistry, University of California, Davis, 95616, USA
    J Med Chem 48:4526-34. 2005
    ..In contrast, the most potent member of the correlative group shows behavior consistent with IN being the cellular target...
  72. pmc Ring substituent effects on biological activity of vinyl sulfones as inhibitors of HIV-1
    D Christopher Meadows
    Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
    Bioorg Med Chem 15:1127-37. 2007
    ....
  73. ncbi request reprint Dynamic receptor-based pharmacophore model development and its application in designing novel HIV-1 integrase inhibitors
    Jinxia Deng
    Department of Chemical Engineering, University of Houston, Houston, TX 77204 4004, USA
    J Med Chem 48:1496-505. 2005
    ..Compounds 7 and 18 with IC(50)s of 8 microM and 15 microM, respectively, against the strand transfer reaction were the most potent. Moreover, 7, 8 and 20 showed a 5-fold selectivity for the strand transfer reaction over 3'-processing...
  74. ncbi request reprint Design of novel bioisosteres of beta-diketo acid inhibitors of HIV-1 integrase
    Mario Sechi
    Dipartimento Farmaco Chimico Tossicologico, Universita di Sassari, Sassari, Italy
    Antivir Chem Chemother 16:41-61. 2005
    ..Results suggested that some of the tested compounds could be considered as lead compounds and suitable for further optimization...
  75. ncbi request reprint Naphthoxazepine inhibitors of HIV-1 integrase: synthesis and biological evaluation
    Antonio Garofalo
    Dipartimento di Scienze Farmaceutiche, Universita della Calabria, 87036 Arcavacata di Rende, CS, Italy
    ChemMedChem 3:986-90. 2008
    ..Some of the new derivatives show potency similar to that of the reference compounds, thus gaining further insight into the structure-activity relationship of this class of IN inhibitors...
  76. pmc Effect of HIV integrase inhibitors on the RAG1/2 recombinase
    Meni Melek
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 5, Room 241, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 99:134-7. 2002
    ..These results further underscore the similarities between RAG1/2 and integrase and suggest that certain integrase inhibitors may have the potential to interfere with aspects of B and T cell development...
  77. ncbi request reprint Sequence-based design and discovery of peptide inhibitors of HIV-1 integrase: insight into the binding mode of the enzyme
    Hui Yuan Li
    State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, CAS, 555 Zuchongzhi Road, Shanghai 201203, China
    J Med Chem 49:4477-86. 2006
    ....
  78. ncbi request reprint Synthesis, anti-HIV-1 integrase, and cytotoxic activities of 4-chloro-N-(4-oxopyrimidin-2-yl)-2-mercaptobenzenesulfonamide derivatives
    Zdzisław Brzozowski
    Department of Chemical Technology of Drugs, Medical University of Gdansk, Al Gen Hallera 107, 80 416 Gdansk, Poland
    Eur J Med Chem 43:1188-98. 2008
    ..The compounds 26-28 were inactive, whereas the other compounds exhibited high or reasonable activity (GI(50)<0.01-20.0 microM) against one or more human tumor cell lines...
  79. ncbi request reprint Beta-diketo acids with purine nucleobase scaffolds: novel, selective inhibitors of the strand transfer step of HIV integrase
    Vasu Nair
    The Center for Drug Discovery and the Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA
    Bioorg Med Chem Lett 16:1920-3. 2006
    ..In the work focused on the discovery of inhibitors of HIV integrase, we have synthesized new beta-diketo acids with purine nucleobase scaffolds that are potent inhibitors of the strand transfer steps of wild-type HIV-1 integrase...
  80. ncbi request reprint Codon-optimized cloning, expression and characertization of the C-terminal region of human apoptotic protein GADD34 in Escherichia coli
    Ping Yu
    Protein nucleic acid interactions section, Structural Biophysics Laboratory, NCI Frederick, Frederick, Maryland 21702, USA
    Cell Cycle 3:75-9. 2004
    ....
  81. ncbi request reprint De novo design and synthesis of HIV-1 integrase inhibitors
    Mahindra T Makhija
    Pharmaceutical Division, Department of Chemical Technology, University of Mumbai, Matunga, Mumbai 400019, India
    Bioorg Med Chem 12:2317-33. 2004
    ..Nonetheless, these compounds possess structural features not seen in known HIV-1 integrase inhibitors and thus can serve as excellent leads for further optimization of anti-HIV-1 integrase activity...
  82. doi request reprint Evaluation of biodistribution and anti-tumor effect of a dimeric RGD peptide-paclitaxel conjugate in mice with breast cancer
    Qizhen Cao
    Molecular Imaging Program at Stanford, Department of Radiology, Biophysics, and Bio X Program, Stanford University School of Medicine, 1201 Welch Rd, Stanford P095, CA 94305 5484, USA
    Eur J Nucl Med Mol Imaging 35:1489-98. 2008
    ..In this study, we evaluated the anti-tumor efficacy of a dimeric RGD peptide-paclitaxel conjugate (RGD2-PTX) in an orthotopic MDA-MB-435 breast cancer model...
  83. ncbi request reprint Identification of N-phenyl-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as a new class of HIV-1 entry inhibitors that prevent gp120 binding to CD4
    Qian Zhao
    Laboratory of Molecular Modeling and Drug Design of the Lindsley F Kimball Research Institute of The New York Blood Center, 310 E 67th Street, New York, NY 10021, USA
    Virology 339:213-25. 2005
    ....
  84. ncbi request reprint Inhibition of the strand transfer step of HIV-1 integrase by non-natural dinucleotides
    Guochen Chi
    Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA
    Bioorg Med Chem Lett 14:4815-7. 2004
    ..To the best of our knowledge, these compounds represent only the second example of selective strand transfer inhibitors of HIV integrase...

Research Grants4

  1. Integrin avb3 targeted drug design, delivery, and imaging
    Nouri Neamati; Fiscal Year: 2007
    ..Because most solid tumors are angiogenesis dependent and express integrin on their cell surface, drugs developed in this project are also applicable to many other tumor types such as brain, breast, ovarian, prostate, and colon cancer. ..
  2. Integrin avb3 targeted drug design, delivery, and imaging
    Nouri Neamati; Fiscal Year: 2009
    ..Because most solid tumors are angiogenesis dependent and express integrin on their cell surface, drugs developed in this project are also applicable to many other tumor types such as brain, breast, ovarian, prostate, and colon cancer. ..
  3. Integrin avb3 targeted drug design, delivery, and imaging
    Nouri Neamati; Fiscal Year: 2010
    ..Because most solid tumors are angiogenesis dependent and express integrin on their cell surface, drugs developed in this project are also applicable to many other tumor types such as brain, breast, ovarian, prostate, and colon cancer. ..