GRL-02031, a novel nonpeptidic protease inhibitor (PI) containing a stereochemically defined fused cyclopentanyltetrahydrofuran potent against multi-PI-resistant human immunodeficiency virus type 1 in vitro

Antimicrobial Agents and Chemotherapy

Volumn 53, Issue 3, 2009, Pages 997-1006

  Koh, Yasuhiro ^a   Das, Debananda ^b   Leschenko, Sofiya ^c   Nakata, Hirotomo ^a,b   Ogata Aoki, Hiromi ^a   Amano, Masayuki ^a   Nakayama, Maki ^a   Ghosh, Arun K ^c   Mitsuya, Hiroaki ^a,b  

^a KUMAMOTO UNIVERSITY   (Japan)

^b NATIONAL CANCER INSTITUTE   (United States)

^c PURDUE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMPRENAVIR; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; ATAZANAVIR; CYCLOPENTANYLTETRAHYDROFURAN; GRL 02031; INDINAVIR; LOPINAVIR; NELFINAVIR; PROTEINASE; PROTEINASE INHIBITOR; RITONAVIR; SAQUINAVIR; TETRAHYDROFURAN DERIVATIVE; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ANTIVIRAL RESISTANCE; ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; DRUG MECHANISM; GENE MUTATION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; IN VITRO STUDY; PRIORITY JOURNAL; STEREOCHEMISTRY; VIRUS REPLICATION; VIRUS STRAIN;

AMINO ACID SEQUENCE; CARBAMATES; CYCLOPENTANES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG RESISTANCE, VIRAL; FURANS; HIV PROTEASE INHIBITORS; HIV-1; HUMANS; INHIBITORY CONCENTRATION 50; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MOLECULAR STRUCTURE; SULFONAMIDES;

EID: 62949083325     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00689-08     Document Type: Article

References (49)

1. Amano, M., Y. Koh, D. Das, J. Li, S. Leschenko, Y. F. Wang, P. I. Boross, I. T. Weber, A. K. Ghosh, and H. Mitsuya. 2007. A novel bis-tetrahydrofura-nylurethane-containing nonpeptidic protease inhibitor (PI), GRL-9S065. is potent against multiple-PI-resistant human immunodeficiency virus in vitro. Antimicrob. Agents Chemother. 51:2143-2155.
2. Antiretroviral Therapy Cohort Collaboration. 2008. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet 372:293-299.
3. Bhaskaran, K., O, Hamouda, M. Sannes, F. Boufassa, A. M. Johnson, P. C. Lambert, and K. Porter. 2008. Changes in the risk of death after HIV seroconversion compared with mortality in the general population. JAMA 300:51-59.
4. Cho, A. E., V. Guallar, B. J. Berne, and R. Friesner. 2005. Importance of accurate charges in molecular docking: quantum mechanical/molecular mechanical (QM/MM) approach. J. Comput. Chem. 26:915-931.
5. Clotet, B., N. Bellos, J. M. Molina, D. Cooper, J. C. Goffard, A. Lazzarin, A. Wohrmann, C. Katlama, T. Wilkin, R. Haubrich, C. Cohen, C. Farthing, D. Jayaweera, M. Markowitz, P. Ruane, S. Spinosa-Guzman, and E. Lefebvre. 2007. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials. Lancet 369:1169-1178.
6. Condra, J. H., W. A. Schleif, O. M. Blahy, L. J. Gabryelski, D. J. Graham, J. C. Quintero, A. Rhodes, H. L. Robbins, E. Roth, M. Shivaprakash, et al. 1995. In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors. Nature 374:569-571.
7. De Clercq, E. 2002. Strategies in the design of antiviral drugs. Nat. Rev. Drug Discov. 1:13-25.
8. de Mendoza, C, and V. Soriano. 2004. Resistance to HIV protease inhibitors: mechanisms and clinical consequences. Curr. Drug Metab. 5:321-328.
9. De Meyer, S., H. Azijn, D. Surleraux, D. Jochmans, A. Tahri, R. Pauwels, P. Wigerinck, and M. P. de Bethune. 2005. TMC114, a novel human immunodeficiency vims type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob. Agents Chemother. 49:2314-2321.
10. Erickson, J. W., and S. K. Burt 1996. Structural mechanisms of HIV drug resistance. Annu. Rev. Pharmacol. Toxicol. 36:545-571.
11. Ferrer, E., D. Podzamczer, M. Arnedo, E. Fumero, P. McKenna, A. Rinehart, J. L. Perez, M. J. Barbera, T. Pumarola, J. M. Gatell, and F. Gudiol. 2003. Genotype and phenotype at baseline and at failure in human immunodeficiency virus-infected antiretroviral-naive patients in a randomized trial comparing zidovudine and lamivudine plus nelfinavir or nevirapine. J. Infect. Dis. 187:687-690.
12. Friesner, R. A., J. L. Banks, R. B. Murphy, T. A. Halgren, J. J. Klicic, D. T. Mainz, M. P. Repasky, E. H. Knoll, M. Shelley, J. K. Perry, D. E. Shaw, P. Francis, and P. S. Shenkin, 2004. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem. 47:1739-1749.
13. Friesner, R. A., R. B. Murphy, M. P. Repasky, L. L. Frye, J. R. Greenwood, T. A. Halgren, P. C. Sanschagrin, and D. T. Mainz. 2006. Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J. Med. Chem. 49:6177-6196.
14. Gatanaga, H., Y. Suzuki, H. Tsang, K. Yoshimura, M. F. Kavlick, K. Na-gashima, R. J. Gorelick, S. Mardy, C. Tang, M. F. Summers, and H. Mit-suya. 2002. Amino acid substitutions in Gag protein at non-cleavage sites are indispensable for the development of a high multitude of HIV-1 resistance against protease inhibitors. J. Biol. Chem. 277:5952-5961.
15. Ghosh, A. K., B. D. Chapsal, I. T. Weber, and H. Mitsuya. 2008. Design of HIV protease inhibitors targeting protein backbone: an effective strategy for combating drug resistance. Acc. Chem. Res. 41:78-86.
16. Ghosh, A. K, P. R Sridhar, S. Leshchenko, A. K. Hussain, J. Li, A. Y. Kovalevsky, D. E. Walters, J. E. Wedekind, V. Grum-Tokars, D. Das, Y. Koh, K. Maeda, H. Gatanaga, I. T. Weber, and H. Mitsuya. 2006. Stucture-based design of novel HIV-1 protease inhibitors to combat drug resistance. J. Med. Chem. 49:5252-5261.
17. Gong, Y. F., B. S. Robinson, R E. Rose, C. Deminie, T. P. Spicer, D. Stock, R. J. Colonno, and P. F. Lin. 2000. In vitro resistance profile of the human immunodeficiency virus type 1 protease inhibitor BMS-232632. Antimicrob. Agents Chemother. 44:2319-2326.
18. Gupta, R., A. Hill, A. W. Sawyer, and D. Pillay. 2008. Emergence of drug resistance in HIV type 1-infected patients after receipt of first-line highly active antiretroviral therapy: a systematic review of clinical trials. Clin. Infect. Dis. 47:712-722.
19. Hertogs, K., S. Bloor, S. D. Kemp, C. Van den Eynde, T. M. Alcorn, R. Pauwels, M. Van Houtte, S. Staszewski, V. Miller, and B. A. Larder. 2000. Phenotypic and genotypic analysis of clinical HIV-1 isolates reveals extensive protease inhibitor cross-resistance: a survey of over 6000 samples. AIDS 14:1203-1210.
20. Hicks, C. B., P. Cahn, D. A. Cooper, S. L. Walmsley, C. Katlama, B. Clotet, A. Lazzarin, M. A. Johnson, D. Neubacher, D. Mayers, and H. Valdez. 2006. Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatment-experienced H1V-1-infected patients at 48 weeks in the Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST) studies: an analysis of combined data from two randomised open-label trials. Lancet 368:466-75.
21. Jacobsen, H., K. Yasargil, D. L. Winslow, J. C. Craig, A. Krohn, I. B. Duncan, and J. Mous. 1995. Characterization of human immunodeficiency virus type 1 mutants with decreased sensitivity to proteinase inhibitor Ro 31-8959. Virology 206:527-534.
22. Kantor, R., W. J. Fessel, A. R. Zolopa, D. Israelski, N. Shulman, J. G. Montoya, M. Harbour, J. M, Schapiro, and R. W, Shafer. 2002. Evolution of primary protease inhibitor resistance mutations during protease inhibitor salvage therapy. Antimicrob. Agents Chemother. 46:1086-1092.
23. Kaplan, A. H., S. F, Michael, R, S. Wehbie, M. F. Knigge, D. A, Paul, L. Everitt, D. J. Kempf, D. W. Norbeck, J. W. Erickson, and R. Swanstrom. 1994. Selection of multiple human immunodeficiency virus type 1 variants that encode viral proteases with decreased sensitivity to an inhibitor of the viral protease. Proc. Natl. Acad. Sci. USA 91:5597-5601.
24. Kemper, C. A., M. D. Witt, P. H. Keiser, M. P. Dube, D. N. Forthal, M. Leibowitz, D. S. Smith, A. Rigby, N. S. Hellmann, Y. S. Lie, J. Leedom, D. Richman, J. A. McCutchan, and R. Haubrich. 2001. Sequencing of protease inhibitor therapy: insights from an analysis of HIV phenotypic resistance in patients failing protease inhibitors. AIDS 15:609-615.
25. Koh, Y., S. Matsumi, D. Das, M. Amano, D. A. Davis, J. Li, S. Leschenko, A. Baldridge, T. Shioda, R. Yarchoan, A. K. Ghosh, and H. Mitsuya. 2007. Potent inhibition of HIV-1 replication by novel non-peptidyl small molecule inhibitors of protease dimerization. J. Biol. Chem. 282:28709-28720.
26. Koh, Y., H. Nakata, K. Maeda, H. Ogata, G. Biker, T. Devasamudram, J. F. Kincaid, P. Boross, Y. F. Wang, Y. Tie, P. Volarath, L. Gaddis, R. W. Harrison, L T. Weber, A. K. Ghosh, and H. Mitsuya. 2003. Novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI) UIC-94017 (TMC114) with potent activity against multi-PI-resistant human immunodeficiency virus in vitro. Antimicrob. Agents Chemother. 47:3123-3129.
27. Li, F., R. Goila-Gaur, K. Salzwedel, N. R. Kilgore, M. Reddick, C. Matal-lana, A. Castillo, D. Zoumplis, D. E. Martin, J. M. Orenstein, G. P. Allaway, E. O. Freed, and C. T. Wild. 2003. PA-457: a potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing. Proc. Natl. Acad. Sci. USA 100:13555-13560.
28. Little, S. J., S. Holte, J. P. Routy, E. S. Daar, M. Markowitz, A. C. Collier, R. A. Koup, J. W. Mellors, E. Connick, B. Conway, M. Kilby, L. Wang, J. M. Whitcomb, N. S. Hellmann, and D. D. Richman. 2002. Antiretroviral-drug resistance among patients recently infected with HIV. N. Engl. J. Med. 347:385-394.
29. Maeda, K., H. Nakata, Y. Koh, T. Miyakawa, H. Ogata, Y. Takaoka, S. Shibayama, K. Sagawa, D. Fukushima, J. Moravek, Y. Koyanagi, and H. Mitsuya. 2004. Spirodiketopiperazine-based CCR5 inhibitor which preserves CC-chemokine/CCR5 interactions and exerts potent activity against R5 human immunodeficiency virus type 1 in vitro. J. Virol. 78:8654-8662.
30. Maeda, K., K. Yoshimura, S. Shibayama, H. Habashita, H. Tada, K. Sagawa, T. Miyakawa, M. Aoki, D. Fukushima, and H. Mitsuya. 2001. Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5 HIV-1 infection through their antagonistic effects on CCR5. J. Biol. Chem. 276:35194-35200.
31. Maguire, M., D. Shortino, A. Klein, W. Harris, V. Manohitharajah, M. Tisdale, R. Elston, J. Yeo, S. Randall, F. Xu, H. Parker, J. May, and W. Snowden. 2002. Emergence of resistance to protease inhibitor amprenavir in human immunodeficiency virus type 1-infected patients: selection of four alternative viral protease genotypes and influence of viral susceptibility to coadministered reverse transcriptase nucleoside inhibitors. Antimicrob. Agents Chemother. 46:731-738.
32. Mammano, F., V. Trouplin, V. Zennou, and F. Clavel. 2000. Retracing the evolutionary pathways of human immunodeficiency virus type 1 resistance to protease inhibitors: virus fitness in the absence and in the presence of drug. J. Virol. 74:8524-8531.
33. McCallister, S., V. Kohlbrenner, K. Squires, A. Lazzarin, P. Kumar, E. Dejesus, J. Nadler, J. Gallant, S. Walmsley, P. Yeni, J. Leith, C. Dohnanyi, D. Hall, J. Sabo, T. MacGregor, W. Verbiest, P. McKenna, and D. Mayers. 2003. Characterization of the impact of genotype, phenotype, and inhibitory quotient on antiviral activity of tipranavir in highly treatment-experienced patients. Antivir. Ther. 8:S15.
34. Melamed, D., M. Mark-Danieli, M. Kenan-Eichler, O. Kraus, A. Castiel, N. Laham, T. Pupko, F. Glaser, N. Ben-Tal, and E. Bacharach. 2004. The conserved carboxy terminus of the capsid domain of human immunodeficiency virus type 1 Gag protein is important for virion assembly and release. J. Virol. 78:9675-9688.
35. Mitsuya, H., and J. Erickson. 1999. Discovery and development of antiret-roviral therapeutics for HIV infection, p. 751-780. In T. C. Merigan, J. G. Bartlet, and D. Bolognesi (ed.). Textbook of AIDS medicine. The Williams & Wilkins Co., Baltimore, MD.
36. Mitsuya, H., K. Maeda, D. Das, and A. K. Ghosh. 2008. Development of protease inhibitors and the fight with drug-resistant HIV-1 variants. Adv. Pharmacol. 56:169-197.
37. Molla, A., M. Korneyeva, Q. Gao, S. Vasavanonda, P. J. Schipper, H. M. Mo, M. Markowitz, T. Chernyavskiy, P. Niu, N. Lyons, A. Hsu, G. R. Granneman, D. D. Ho, C. A. Boucher, J. M. Leonard, D. W. Norbeck, and D. J. Kempf. 1996. Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Nat. Med. 2:760-766.
38. Murphy, E. L., A. C. Collier, L. A. Kalish, S. F. Assmann, M. F. Para, T. P. Flanigan, P. N. Kumar, L. Mintz, F. R. Wallach, and G. J. Nemo. 2001. Highly active antiretroviral therapy decreases mortality and morbidity in patients with advanced HIV disease. Ann. Intern. Med. 135:17-26.
39. Murphy, R. L. 2000. New antiretroviral drugs in development. AIDS 14(Suppl. 3):S227-S234.
40. Partaledis, J. A., K. Yamaguchi, M. Tisdale, E. E. Blair, C. Falcione, B. Maschera, R. E. Myers, S. Pazhanisamy, O. Futer, A. B. Cullinan, C. M. Stuver, R. A. Byrn, and D. J. Livingston. 1995. In vitro selection and characterization of human immunodeficiency virus type 1 (HIV-1) isolates with reduced sensitivity to hydroxyethylamino sulfonamide inhibitors of HIV-1 aspartyl protease. J. Virol. 69:5228-5235.
41. Patick, A. K., M. Duran, Y. Cao, D. Shugarts, M. R. Keller, E. Mazabel, M. Knowles, S. Chapman, D. R. Kuritzkes, and M. Markowitz. 1998. Genotypic and phenotypic characterization of human immunodeficiency virus type 1 variants isolated from patients treated with the protease inhibitor nelfinavir. Antimicrob. Agents Chemother. 42:2637-2644.
42. Prado, J. G., T. Wrin, J. Beauchaine, L. Ruiz, C. J. Petropoulos, S. D. Frost, B. Clotet, R. T. D'Aquila, and J. Martinez-Picado. 2002. Amprenavir-resistant HIV-1 exhibits lopinavir cross-resistance and reduced replication capacity. AIDS 16:1009-1017.
43. Rodriguez-Barrios, F., and F. Gago. 2004. HIV protease inhibition: limited recent progress and advances in understanding current pitfalls. Curr. Top. Med. Chem. 4:991-1007.
44. Salzwedel, K., R. Goila-Gaur, C. Adamson, F. Li, A. Castillo, N. Kilgore, M. Red dick, C. Matallana, D. Zoumplis, D. Martin, G. Allaway, E. Freed, and C. Wild. 2004. Selection for and characterization of HIV-1 isolates resistant to the maturation inhibitor PA-457. Antivir. Ther. 9:S8.
45. Shirasaka, T., M. F. Kavlick, T. Ueno, W. Y. Gao, E. Kojima, M. L. Alcaide, S. Chokekijehai, B. M. Roy, E. Arnold, R. Yarchoan, et al. 1995. Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. Proc. Natl. Acad. Sci. USA 92:2398-23402.
46. Walensky, R. P., A. D. Paltiel, E. Losina, L. M. Mercincavage, B. R. Schack-man, P. E. Sax, M. C. Weinstein, and K. A. Freedberg. 2006. The survival benefits of AIDS treatment in the United States. J. Infect. Dis. 194:11-19.
47. Yoshimura, K., R. Kato, M. F. Kavlick, A. Nguyen, V. Maroun, K. Maeda, K. A. Hussain, A. K. Ghosh, S. V. Gulnik, J. W. Erickson, and H. Mitsuya. 2002. A potent human immunodeficiency virus type 1 protease inhibitor, U1C-94003 (TMC-126), and selection of a novel (A28S) mutation in the protease active site. J. Virol. 76:1349-1358.
48. Yoshimura, K., R. Kato, K. Yusa, M. F. Kavlick, V. Maroun, A. Nguyen, T. Mimoto, T. Ueno, M. Shintani, J. Falloon, H. Masur, H. Hayashi, J. Erickson, and H. Mitsuya. 1999. JE-2147: a dipeptide protease inhibitor (PI) that potently inhibits multi-Pi-resistant HIV-1. Proc. Natl. Acad. Sci. USA 96: 8675-8680.
49. Zhou, J., X. Yuan, D. Dismuke, B. M. Forshey, C. Lundquist, K. H. Lee, C. Aiken, and C. H. Chen. 2004. Small-molecule inhibition of human immunodeficiency virus type 1 replication by specific targeting of the final step of virion maturation. J. Virol. 78:922-929.