protease inhibitors


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

Top Publications

  1. Koistinen H, Hekim C, Wu P, Närvänen A, Stenman U. Evaluation of peptides as protease inhibitors and stimulators. Methods Mol Biol. 2014;1088:147-58 pubmed publisher
    ..We also describe graphical analysis of the IC50-value, the effect of a peptide on Michaelis-Menten constant (K(m)) and the maximal reaction rate (V(max)). ..
  2. Cassol E, Misra V, Holman A, Kamat A, Morgello S, Gabuzda D. Plasma metabolomics identifies lipid abnormalities linked to markers of inflammation, microbial translocation, and hepatic function in HIV patients receiving protease inhibitors. BMC Infect Dis. 2013;13:203 pubmed publisher
  3. Palanisamy N, Danielsson A, Kokkula C, Yin H, Bondeson K, Wesslén L, et al. Implications of baseline polymorphisms for potential resistance to NS3 protease inhibitors in Hepatitis C virus genotypes 1a, 2b and 3a. Antiviral Res. 2013;99:12-7 pubmed publisher
    The future interferon-free treatment of hepatitis C virus (HCV) infection could include NS3 protease inhibitors (PIs) for potent pan-genotypic effect...
  4. Thomas D, Bartlett J, Peters M, Sherman K, Sulkowski M, Pham P. Provisional guidance on the use of hepatitis C virus protease inhibitors for treatment of hepatitis C in HIV-infected persons. Clin Infect Dis. 2012;54:979-83 pubmed publisher
    In May 2011, hepatitis C virus (HCV) protease inhibitors (PIs) were approved by the US Food and Drug Administration to treat persons with genotype 1 chronic hepatitis C virus (HCV) infection, but not those dually infected with human ..
  5. Wolf E, Zeißler A, Vosyka O, Zeiler E, Sieber S, Verhelst S. A new class of rhomboid protease inhibitors discovered by activity-based fluorescence polarization. PLoS ONE. 2013;8:e72307 pubmed publisher
    ..Overall, these molecules represent a new scaffold for future inhibitor and activity-based probe development, whereas the assay will allow inhibitor screening of ill-characterized membrane proteases. ..
  6. Samanta S, Lim T, Lam Y. Synthesis and in vitro evaluation of West Nile virus protease inhibitors based on the 2-{6-[2-(5-phenyl-4H-{1,2,4]triazol-3-ylsulfanyl)acetylamino]benzothiazol-2-ylsulfanyl}acetamide scaffold. ChemMedChem. 2013;8:994-1001 pubmed publisher
    ..Molecular docking of 1 a24 into the WNV protease showed that the compound interferes with productive interactions of the NS2B cofactor with the NS3 protease and is an allosteric inhibitor of the WNV NS3 protease. ..
  7. Samanta S, Cui T, Lam Y. Discovery, synthesis, and in vitro evaluation of West Nile virus protease inhibitors based on the 9,10-dihydro-3H,4aH-1,3,9,10a-tetraazaphenanthren-4-one scaffold. ChemMedChem. 2012;7:1210-6 pubmed publisher
  8. Thompson A, Locarnini S, Beard M. Resistance to anti-HCV protease inhibitors. Curr Opin Virol. 2011;1:599-606 pubmed publisher
    The era of direct acting antiviral therapy for HCV infection has dawned with the recent approval of the NS3 protease inhibitors telaprevir and boceprevir...
  9. Pascale A, Serfaty L. Triple therapy with first generation HCV protease inhibitors: lead-in or no lead-in phase?. J Hepatol. 2013;58:391-4 pubmed publisher
    ..C virus (HCV) is the triple therapy combining pegylated interferon (PEG-IFN), ribavirin (RBV)and NS3/NS4 protease inhibitors, boceprevir or telaprevir [1]...

More Information


  1. Kato M, Leite A, Hannas A, Calabria M, Magalhaes A, Pereira J, et al. Impact of protease inhibitors on dentin matrix degradation by collagenase. J Dent Res. 2012;91:1119-23 pubmed publisher
    ..whether the reduction of the degradation of the demineralized organic matrix (DOM) by pre-treatment with protease inhibitors (PI) is effective against dentin matrix loss. Bovine dentin slices were demineralized with 0...
  2. Ferenci P, Reddy K. Impact of HCV protease-inhibitor-based triple therapy for chronic HCV genotype 1 infection. Antivir Ther. 2011;16:1187-201 pubmed publisher
    Boceprevir and telaprevir are the first HCV protease inhibitors to be approved for the treatment of chronic hepatitis C genotype 1 infection...
  3. Romano K, Ali A, Aydin C, Soumana D, Ozen A, Deveau L, et al. The molecular basis of drug resistance against hepatitis C virus NS3/4A protease inhibitors. PLoS Pathog. 2012;8:e1002832 pubmed publisher
    ..Despite extensive efforts to develop more potent next-generation protease inhibitors, however, the long-term efficacy of this drug class is challenged by the rapid emergence of resistance...
  4. Hayashi N, Okanoue T, Tsubouchi H, Toyota J, Chayama K, Kumada H. Efficacy and safety of telaprevir, a new protease inhibitor, for difficult-to-treat patients with genotype 1 chronic hepatitis C. J Viral Hepat. 2012;19:e134-42 pubmed publisher
    ..Telaprevir in combination with PEG-IFN/RBV led to a high SVR rate for relapsers and may offer a potential new therapy for nonresponders even with a shorter treatment period. ..
  5. Sarrazin C, Hezode C, Zeuzem S, Pawlotsky J. Antiviral strategies in hepatitis C virus infection. J Hepatol. 2012;56 Suppl 1:S88-100 pubmed publisher
    ..Two NS3/4A protease inhibitors, telaprevir and boceprevir, were approved in Europe and the United States in 2011 in combination with ..
  6. Islam F, Wu J, Jansson J, Wilson D. Relative risk of cardiovascular disease among people living with HIV: a systematic review and meta-analysis. HIV Med. 2012;13:453-68 pubmed publisher
    ..Although effective in prolonging survival, ART (in particular PI-based regimens) is related to further increased risk of CVD events among people at highest initial absolute risk of cardiovascular disease. ..
  7. Lin Y, Chang Y, Hsiao N, Hsieh J, Wang C, Kung S, et al. Fisetin and rutin as 3C protease inhibitors of enterovirus A71. J Virol Methods. 2012;182:93-8 pubmed publisher
    ..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. ..
  8. Chauhan D, Tian Z, Nicholson B, Kumar K, Zhou B, Carrasco R, et al. A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance. Cancer Cell. 2012;22:345-58 pubmed publisher
    ..Our preclinical study therefore supports clinical evaluation of USP7 inhibitor, alone or in combination, as a potential MM therapy. ..
  9. Santos A, Braga Silva L. Aspartic protease inhibitors: effective drugs against the human fungal pathogen Candida albicans. Mini Rev Med Chem. 2013;13:155-62 pubmed
    ..albicans Saps as well as the blockage of several biological processes controlled by these proteolytic enzymes. The present article will discuss the updates on the functional implications of HIV PIs on the development of candidiasis. ..
  10. Hulskotte E, Feng H, Xuan F, van Zutven M, Treitel M, Hughes E, et al. Pharmacokinetic interactions between the hepatitis C virus protease inhibitor boceprevir and ritonavir-boosted HIV-1 protease inhibitors atazanavir, darunavir, and lopinavir. Clin Infect Dis. 2013;56:718-26 pubmed publisher study to assess the pharmacokinetic interactions between boceprevir and ritonavir-boosted protease inhibitors (PI/r) was conducted in 39 healthy adults...
  11. Wartelle Bladou C, Le Folgoc G, Bourliere M, Lecomte L. Hepatitis C therapy in non-genotype 1 patients: the near future. J Viral Hepat. 2012;19:525-36 pubmed publisher
    ..DAAs comprise so far first-generation, second-wave and second-generation NS3/4A protease inhibitors (PIs), nucleos(t)ide (NIs) and non-nucleoside inhibitors of the NS5B RNA polymerase and NS5A complex ..
  12. Pearlman B. Protease inhibitors for the treatment of chronic hepatitis C genotype-1 infection: the new standard of care. Lancet Infect Dis. 2012;12:717-28 pubmed publisher
    ..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 ..
  13. Cooper C. Hepatitis C treatment highlights from the 2011 American Association for the Study of Liver Disease meeting. Clin Infect Dis. 2012;55:418-25 pubmed publisher
    ..Expertise in HCV antiviral resistance, drug metabolism, and drug-drug interactions and optimization of drug adherence are now key requirements in the DAA era. ..
  14. Gard P, Naylor C, Ali S, Partington C. Blockade of pro-cognitive effects of angiotensin IV and physostigmine in mice by oxytocin antagonism. Eur J Pharmacol. 2012;683:155-60 pubmed publisher
  15. Kim J, Culley C, Mohammad R. Telaprevir: an oral protease inhibitor for hepatitis C virus infection. Am J Health Syst Pharm. 2012;69:19-33 pubmed publisher
    ..Telaprevir, an HCV NS3/4A protease inhibitor, has been shown to be effective in increasing SVR rates when used with peginterferon alfa and ribavirin in patients with chronic HCV genotype 1 infection, regardless of treatment history. ..
  16. Xue Y, Ha Y. Catalytic mechanism of rhomboid protease GlpG probed by 3,4-dichloroisocoumarin and diisopropyl fluorophosphonate. J Biol Chem. 2012;287:3099-107 pubmed publisher
    ..Combining the new structural data with those on the isocoumarin complex sheds further light on the plasticity of the active site of rhomboid membrane protease...
  17. Scherrer A, Böni J, Yerly S, Klimkait T, Aubert V, Furrer H, et al. Long-lasting protection of activity of nucleoside reverse transcriptase inhibitors and protease inhibitors (PIs) by boosted PI containing regimens. PLoS ONE. 2012;7:e50307 pubmed publisher
    ..Thus, more options remain for second-line therapy. This finding is potentially of high relevance, in particular for settings with poor or lacking virological monitoring. ..
  18. Suzuki F, Sezaki H, Akuta N, Suzuki Y, Seko Y, Kawamura Y, et al. Prevalence of hepatitis C virus variants resistant to NS3 protease inhibitors or the NS5A inhibitor (BMS-790052) in hepatitis patients with genotype 1b. J Clin Virol. 2012;54:352-4 pubmed publisher
    ..To detect HCV variants resistant to NS3 protease inhibitors or the NS5A inhibitor (BMS-790052) in hepatitis patients infected with HCV-1b...
  19. Kwong A, Kauffman R, Hurter P, Mueller P. Discovery and development of telaprevir: an NS3-4A protease inhibitor for treating genotype 1 chronic hepatitis C virus. Nat Biotechnol. 2011;29:993-1003 pubmed publisher
    ..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. ..
  20. Schiering N, D Arcy A, Villard F, Simic O, Kamke M, Monnet G, et al. A macrocyclic HCV NS3/4A protease inhibitor interacts with protease and helicase residues in the complex with its full-length target. Proc Natl Acad Sci U S A. 2011;108:21052-6 pubmed publisher
    ..First-generation NS3/4A protease inhibitors have recently been introduced into clinical practice, markedly changing HCV treatment options...
  21. Sitole M, Silva M, Spooner L, Comee M, Malloy M. Telaprevir versus boceprevir in chronic hepatitis C: a meta-analysis of data from phase II and III trials. Clin Ther. 2013;35:190-7 pubmed publisher
    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 ..
  22. Xue Y, Chowdhury S, Liu X, Akiyama Y, ELLMAN J, Ha Y. Conformational change in rhomboid protease GlpG induced by inhibitor binding to its S' subsites. Biochemistry. 2012;51:3723-31 pubmed publisher
    ..This study, together with earlier crystallographic investigation of smaller inhibitors, suggests a simple model for explaining substrate binding to rhomboid protease. ..
  23. Esteban R, Buti M. Triple therapy with boceprevir or telaprevir for treatment naïve HCV patients. Best Pract Res Clin Gastroenterol. 2012;26:445-53 pubmed publisher
    Boceprevir and telaprevir are the first two protease inhibitors available for the treatment of patients infected with HCV genotype 1...
  24. Chayama K, Hayes C, Ohishi W, Kawakami Y. Treatment of chronic hepatitis C virus infection in Japan: update on therapy and guidelines. J Gastroenterol. 2013;48:1-12 pubmed publisher
    ..Other protease inhibitors with fewer side effects are now in clinical trials in Japan...
  25. Zhang Y, Zhou L, Rouge L, Phillips A, Lam C, Liu P, et al. Conformational stabilization of ubiquitin yields potent and selective inhibitors of USP7. Nat Chem Biol. 2013;9:51-8 pubmed publisher
  26. Lim S, Qin X, Susser S, Nicholas J, Lange C, Herrmann E, et al. Virologic escape during danoprevir (ITMN-191/RG7227) monotherapy is hepatitis C virus subtype dependent and associated with R155K substitution. Antimicrob Agents Chemother. 2012;56:271-9 pubmed publisher
    ..These data indicate the ascendant importance of R155K for viral escape during danoprevir treatment and may have implications for the clinical use of this agent...
  27. Calugi C, Guarna A, Trabocchi A. Insight into the structural similarity between HIV protease and secreted aspartic protease-2 and binding mode analysis of HIV-Candida albicans inhibitors. J Enzyme Inhib Med Chem. 2013;28:936-43 pubmed publisher
    ..HIV-1 protease inhibitors herein investigated can fit the active site of Sap2, adopting very similar ligand-backbone conformations...
  28. Cento V, Mirabelli C, Salpini R, Dimonte S, Artese A, Costa G, et al. HCV genotypes are differently prone to the development of resistance to linear and macrocyclic protease inhibitors. PLoS ONE. 2012;7:e39652 pubmed publisher
    ..Overall, this can account for different responsiveness of HCV-genotypes to PIs, with important clinical implications in tailoring individualized and appropriate regimens. ..
  29. Lee H, Torres J, Truong L, Chaudhuri R, Mittal A, Johnson M. Reducing agents affect inhibitory activities of compounds: results from multiple drug targets. Anal Biochem. 2012;423:46-53 pubmed publisher
    ..We demonstrate the feasibility of using GSH for in vitro HTS assays with these three target enzymes. ..
  30. Poordad F, Lawitz E, Kowdley K, Cohen D, Podsadecki T, Siggelkow S, et al. Exploratory study of oral combination antiviral therapy for hepatitis C. N Engl J Med. 2013;368:45-53 pubmed publisher
    ..Funded by Abbott; number, NCT01306617.). ..
  31. Friborg J, Levine S, Chen C, Sheaffer A, Chaniewski S, Voss S, et al. Combinations of lambda interferon with direct-acting antiviral agents are highly efficient in suppressing hepatitis C virus replication. Antimicrob Agents Chemother. 2013;57:1312-22 pubmed publisher
    ..Overall, these data support further clinical development of lambda as part of alternative combination treatments with DAAs for patients chronically infected with HCV. ..
  32. Basler M, Groettrup M. Using protease inhibitors in antigen presentation assays. Methods Mol Biol. 2013;960:31-39 pubmed publisher
    ..Small molecule inhibitors are useful tools for probing the role of proteases in MHC class I antigen processing. Here, we describe different methods to test the impact of protease inhibitors in antigen presentation assays.
  33. Hoffmann L, Ramos J, Souza E, Araújo Ramos A, Villela Nogueira C, Urményi T, et al. Dynamics of resistance mutations to NS3 protease inhibitors in a cohort of Brazilian patients chronically infected with hepatitis C virus (genotype 1) treated with pegylated interferon and ribavirin: a prospective longitudinal study. Virol J. 2013;10:57 pubmed publisher
    ..Mapping NS3 protease resistance mutations to protease inhibitors or anti-viral drug candidates is important to direct anti-HCV drug treatment...
  34. Rodriguez Torres M. Focus on drug interactions: the challenge of treating hepatitis C virus infection with direct-acting antiviral drugs in the HIV-positive patient. Curr Opin Infect Dis. 2013;26:50-7 pubmed publisher
    ..The first-generation of approved HCV DAAs improved efficacy of therapy in coinfected patients, but have multiple safety concerns, including potentially serious drug interactions with ART. Early results from newer DAAs are promising. ..
  35. Zhou L, Barão S, Laga M, Bockstael K, Borgers M, Gijsen H, et al. The neural cell adhesion molecules L1 and CHL1 are cleaved by BACE1 protease in vivo. J Biol Chem. 2012;287:25927-40 pubmed publisher
    ..This work provides molecular insights into the function and the pathways in which BACE1 is involved, and it will help to predict or interpret possible side effects of BACE1 inhibitor drugs in current clinical trials. ..
  36. von Elert E, Zitt A, Schwarzenberger A. Inducible tolerance to dietary protease inhibitors in Daphnia magna. J Exp Biol. 2012;215:2051-9 pubmed publisher
    ..This mechanism might be relevant for the transfer of tolerance to the next generation through maternal effects...
  37. Liu S, Cipriano L, Holodniy M, Owens D, Goldhaber Fiebert J. New protease inhibitors for the treatment of chronic hepatitis C: a cost-effectiveness analysis. Ann Intern Med. 2012;156:279-90 pubmed publisher
    Chronic hepatitis C virus is difficult to treat and affects approximately 3 million Americans. Protease inhibitors increase the effectiveness of standard therapy, but they are costly...
  38. Pimentel Elardo S, Buback V, Gulder T, Bugni T, Reppart J, Bringmann G, et al. New tetromycin derivatives with anti-trypanosomal and protease inhibitory activities. Mar Drugs. 2011;9:1682-97 pubmed publisher
    ..The compounds showed antiparasitic activities against T. brucei and time-dependent inhibition of cathepsin L-like proteases with K(i) values in the low micromolar range...
  39. D Arcy P, Brnjic S, Olofsson M, Fryknäs M, Lindsten K, De Cesare M, et al. Inhibition of proteasome deubiquitinating activity as a new cancer therapy. Nat Med. 2011;17:1636-40 pubmed publisher
    ..Our results show that the deubiquitinating activity of the 19S regulatory particle is a new anticancer drug target. ..
  40. Lawitz E, Poordad F, Kowdley K, Cohen D, Podsadecki T, Siggelkow S, et al. 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. J Hepatol. 2013;59:18-23 pubmed publisher
  41. Paolucci S, Fiorina L, Piralla A, Gulminetti R, Novati S, Barbarini G, et al. Naturally occurring mutations to HCV protease inhibitors in treatment-naïve patients. Virol J. 2012;9:245 pubmed publisher
    b>Protease inhibitors (PIs) to treat hepatitis C (HCV) virus infection have been approved and others are under development...
  42. Wang H, Wang L, Zhou M, Yang M, Ma C, Chen T, et al. Functional peptidomics of amphibian skin secretion: A novel Kunitz-type chymotrypsin inhibitor from the African hyperoliid frog, Kassina senegalensis. Biochimie. 2012;94:891-9 pubmed publisher
    ..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 ..
  43. Gruber V, Rainey P, Moody D, Morse G, Ma Q, Prathikanti S, et al. Interactions between buprenorphine and the protease inhibitors darunavir-ritonavir and fosamprenavir-ritonavir. Clin Infect Dis. 2012;54:414-23 pubmed publisher
    ..buprenorphine, a partial opioid agonist used for opioid dependence treatment and pain management, and the protease inhibitors (PIs) darunavir-ritonavir and fosamprenavir-ritonavir...
  44. Rawlings N, Barrett A, Bateman A. MEROPS: the database of proteolytic enzymes, their substrates and inhibitors. Nucleic Acids Res. 2012;40:D343-50 pubmed publisher
  45. Brinkman D, Jia X, Potriquet J, Kumar D, Dash D, Kvaskoff D, et al. Transcriptome and venom proteome of the box jellyfish Chironex fleckeri. BMC Genomics. 2015;16:407 pubmed publisher
    ..The generated data represent a useful resource to guide future comparative studies, novel protein/peptide discovery and the development of more effective treatments for jellyfish stings in humans. (Length: 300). ..
  46. Tambaro S, Reali R, Volonterio A, Zanda M, Olimpieri F, Pinna G, et al. NESS002ie: a new fluorinated thiol endopeptidase inhibitor with antinociceptive activity in an animal model of persistent pain. Pharmacol Biochem Behav. 2013;110:137-44 pubmed publisher
    ..This significant effect could be due to the replacement of isobutyl chain of the thiol C20 with the trifluoromethyl group. ..
  47. Lorente E, Garcia R, Lopez D. Allele-dependent processing pathways generate the endogenous human leukocyte antigen (HLA) class I peptide repertoire in transporters associated with antigen processing (TAP)-deficient cells. J Biol Chem. 2011;286:38054-9 pubmed publisher
    ..Using different protease inhibitors, four different proteolytic specificities were identified...
  48. Lawitz E, Makara M, Akarca U, Thuluvath P, Preoţescu L, Varunok P, et al. Efficacy and Safety of Ombitasvir, Paritaprevir, and Ritonavir in an Open-Label Study of Patients With Genotype 1b Chronic Hepatitis C Virus Infection With and Without Cirrhosis. Gastroenterology. 2015;149:971-80.e1 pubmed publisher
    ..This regimen was well tolerated and was associated with low rates of treatment discontinuation. no: NCT01685203. ..
  49. Siva V, Wang L, Qiu L, Zhou Z, Liu C, Yang J, et al. Polymorphism in a serine protease inhibitor gene and its association with the resistance of bay scallop (Argopecten irradians) to Listonella anguillarum challenge. Fish Shellfish Immunol. 2016;59:1-8 pubmed publisher
    Serine protease inhibitors (SPIs) play a crucial role in regulation of both host and bacterial serine protease. They are classified into several protein families, where Kazal-type inhibitors are one of families with multi-domain...
  50. Eatemadi A, Aiyelabegan H, Negahdari B, Mazlomi M, Daraee H, Daraee N, et al. Role of protease and protease inhibitors in cancer pathogenesis and treatment. Biomed Pharmacother. 2017;86:221-231 pubmed publisher
    ..On the other hand, protease inhibitors could be considered as a potent strategy in cancer therapy...
  51. Zhu S, Shi Y, Zhang X, Zheng G. Biocatalytic Asymmetric Synthesis of (1R, 2S)-N-Boc-vinyl-ACCA Ethyl Ester with a Newly Isolated Sphingomonas aquatilis. Appl Biochem Biotechnol. 2018;184:500-512 pubmed publisher
    ..vinyl-ACCA) is a key chiral intermediate in the synthesis of highly potent hepatitis C virus (HCV) NS3/4A protease inhibitors such as asunaprevir and simeprevir...
  52. Kraft T, Armstrong C, Heitmeier M, Odom A, Hruz P. The Glucose Transporter PfHT1 Is an Antimalarial Target of the HIV Protease Inhibitor Lopinavir. Antimicrob Agents Chemother. 2015;59:6203-9 pubmed publisher
    ..We have previously shown that HIV protease inhibitors (PIs) act as antagonists of mammalian glucose transporters...
  53. Hayashi N, Nakamuta M, Takehara T, Kumada H, Takase A, Howe A, et al. Vaniprevir plus peginterferon alfa-2b and ribavirin in treatment-naive Japanese patients with hepatitis C virus genotype 1 infection: a randomized phase III study. J Gastroenterol. 2016;51:390-403 pubmed publisher
    ..Vaniprevir is a valuable addition to the therapeutic options available to Japanese patients with HCV genotype 1 infection who are eligible for interferon-based treatment. CLINICALTRIALS. NCT01370642. ..