HIV entry and fusion inhibitors

Expert Opinion on Emerging Drugs

Volumn 9, Issue 1, 2004, Pages 1-7

  Chantry, David ^a,b  

^a ELI LILLY AND COMPANY   (United States)

^b ARRAY BIOPHARMA INC   (United States)

Author keywords

AIDS; CCR5; Chemokine; Co receptor; CXCR4; Enfuvirtide; Fusion inhibitor; HIV

Indexed keywords

1 ACETYL N [3 [4 (4 CARBAMOYLBENZYL) 1 PIPERIDINYL]PROPYL] N (3 CHLORO 4 METHYLPHENYL) 4 PIPERIDINECARBOXAMIDE; 1,1' [1,4 PHENYLENEBIS(METHYLENE)]BIS(1,4,8,11 TETRAAZACYCLOTETRADECANE); ABACAVIR; AMD 070; AMPRENAVIR; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; APLAVIROC; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CCR5 INHIBITOR; CHEMOKINE RECEPTOR CXCR4; CHEMOKINE RECEPTOR CXCR4 INHIBITOR; DELAVIRDINE; DIDANOSINE; EFAVIRENZ; ENFUVIRTIDE; HUMAN IMMUNODEFICIENCY VIRUS FUSION INHIBITOR; INDINAVIR; LAMIVUDINE; MARAVIROC; MONOCLONAL ANTIBODY; N [4 [[[6,7 DIHYDRO 2 (4 METHYLPHENYL) 5H BENZOCYCLOHEPTEN 8 YL]CARBONYL]AMINO]BENZYL] N,N DIMETHYL 2H TETRAHYDROPYRAN 4 AMINIUM CHLORIDE; NEVIRAPINE; PROTEINASE INHIBITOR; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; SAQUINAVIR; STAVUDINE; TNX 355; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZALCITABINE; ZIDOVUDINE;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANEMIA; ANTIBIOTIC RESISTANCE; CENTRAL NERVOUS SYSTEM DISEASE; CLINICAL TRIAL; CONCENTRATION LOSS; CRYSTALLURIA; DEFECATION DISORDER; DIARRHEA; DIZZINESS; DRUG APPROVAL; DRUG EFFECT; DRUG EFFICACY; DRUG TOXICITY; DRY SKIN; FATIGUE; GASTROINTESTINAL SYMPTOM; HAIR LOSS; HEADACHE; HEPATITIS; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HYPERSENSITIVITY; INJECTION SITE REACTION; LACTIC ACIDOSIS; LIVER INJURY; LONG TERM CARE; LOOSE FECES; MORTALITY; MYALGIA; NAUSEA; NEPHROLITHIASIS; NEUROPATHY; NEUTROPENIA; NONHUMAN; PANCREATITIS; PARESTHESIA; PERIORAL PARESTHESIA; PERIPHERAL NEUROPATHY; PERIPHERAL PARESTHESIA; PRURITUS; RASH; REVIEW; SIDE EFFECT; STOMATITIS; TERATOGENICITY; VIRUS CELL INTERACTION; VIRUS INHIBITION; VIRUS REPLICATION;

AMINO ACID MOTIFS; ANIMALS; ANTI-HIV AGENTS; ANTIGENS, CD4; CLINICAL TRIALS; CYCLIC N-OXIDES; DOGS; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; DRUG RESISTANCE, VIRAL; DRUG THERAPY, COMBINATION; HAPLORHINI; HIV ENVELOPE PROTEIN GP41; HIV FUSION INHIBITORS; HIV INFECTIONS; HIV PROTEASE INHIBITORS; HIV-1; HUMANS; MEMBRANE FUSION; MEMBRANE GLYCOPROTEINS; ORGANIC CHEMICALS; PEPTIDE FRAGMENTS; PIPERAZINES; PIPERIDINES; PROTEIN BINDING; PYRIDINES; PYRIMIDINES; RABBITS; RECEPTORS, CCR5; RECEPTORS, CXCR4; REVERSE TRANSCRIPTASE INHIBITORS; SPIRO COMPOUNDS;

EID: 2642524481     PISSN: 14728214     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728214.9.1.1     Document Type: Review

References (38)

1. RAFFANTI S, HAAS DW: Antiretroviral agents. In: Goodman and Gilman's The Pharmacological Basis of Therapeutics. Hardman JG, Limbird LE (Eds), McGraw Hill, New York, USA (2001):1349-1379. An excellent review of HIV pathogenesis and current approaches to treatment.
2. WEISS RA: Gullivers travels in HIV land. Nature (2001) 410:963-967.
3. STANTCHEV TS, BRODER CC: Human immunodeficiency virus type-1 and chemokines: beyond competition for common cellular receptors. Cytokine Growth Factor Rev. (2001) 12:219-243.
4. SAMSON M, LIBERT F, DORANZ BJ et al.: Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature (1996) 382:722-725. This paper describes the protection from HIV infection conferred by the Δ35 mutation in CCR5.
5. DEAN M, CARRINGTON M, WINKLER C et al.: Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study: Science (1996) 273:1856-1862. This paper describes the protection from HIV infection conferred by the Δ35 mutation in CCR5.
6. PIOT P, BARTOS M, GHYS PD, WALKER N, SCHWARTLANDER B: The global impact of HIV/AIDS. Nature (2001) 410:968-973. An interesting review of the global HIV epidemic.
7. NABEL GJ: Challenges and opportunity for development of an HIV vaccine. Nature (2001) 410:1002-1007.
8. OGDEN RT, FLEXNER CW: Protease Inhibitors in the Treatment of AIDS. Marcel Dekker, New York, USA (2001).
9. RICHMAN DD: HIV chemotherapy Nature (2001) 410:995-1001.
10. MCCUNE JM: The dynamics of CD4 T cell depletion in HIV disease. Nature (2001) 410:974-979.
11. HAVLIR DV, RICHMAN DD: Viral dynamics of HIV: implications for drug development and therapeutic strategies. Ann. Intern. Med. (1996) 124:984-994.
12. GUNTHARD HF, WONG JK, IGNACIO CC et al.: Human immunodeficiency virus replication and genotypic resistance in blood and lymph nodes after a year of potent antiretroviral therapy. J. Virol. (1998) 72:2422-2428.
13. WONG JK, HEZAREH M, GUNTHARD HF et al.: Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science (1997) 278:1291-1295.
14. HAVLIR DV, MARSCHNER IC, HIRSCH MS et al.: Maintenance antiretroviral therapies in HIV infected patients with undetectable plasma HIV RNA after triple-drug therapy. AIDS Clinical Trials Group Study 343 Team. N. Engl. J. Med. (1998) 339:1261-1268.
15. + T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat. Med. (1999) 5:512-517.
16. LABONTE J, LEBBOS J, KIRKPATRICK P: Enfuvirtide. Nat. Rev. Drug Discov. (2003) 2:345-346. Reviews the launch of enfuvirtide, the first approved HIV fusion inhibitor.
17. DECLERCQ E: Strategies in the design of anti-retroviral drugs. Nat. Rev. Drug Discov. (2002) 1:13-25.
18. SAAG MS, KILBY JM: HIV-1 and HAART: a time to cure, a time to kill. Nat. Med. (1999) 6:609-611.
19. VOLBERDING PA, DEEKS SG: Antiretroviral therapy for HIV infection: promises and problems. JAMA (1998) 279:1343-1344. Describes the limitations of current antiretroviral therapy.
20. BLAIR WS, LIN PF, MEANWRELL NA, WALLACE OB: HIV-1 entry an expanding portal for drug discovery. Drug Dev. Today (2000) 5:183-194.
21. ECKERT DM, KIM PS: Mechanisms of viral membrane fusion and its inhibition. Annu. Rev. Biochem. (2001) 70:777-810. A thorough review of the mechanism of HIV entry and its implications for drug development.
22. ZHANG W, CANZIANI G, PLUGARIU C et al.: Conformational changes of gp120 in epitopes near the CCR5 binding site are induced by CD4 and a CD4 miniprotein mimetic. Biochemistry (1999) 38:9405-9416.
23. DRAGIC T: An overview of the determinants of CCR5 and CXCR4 coreceptor function. J. Gen. Virol. (2001) 82:1807-1814.
24. WILD CT, SHUGARS DC, GREENWELL TK, MCDANAL CB, MATTHEWS TJ: Peptides corresponding to a predictive alpha-helical domain of human immunodeficiency virus type 1 gp41 are potent inhibitors of virus infection. Proc. Natl. Acad. Sci. USA (1994) 91:9770-9774.
25. LALEZARI JP, HENRY K, O'HEARN M et al. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N. Engl. J. Med. (2003) 348:2175-185.
26. DECLERCQ E: Inhibition of HIV infection by bicyclams, highly potent and specific CXCR4 antagonists. Mol. Pharmacol. (2000) 57:833-839.
27. HENDRIX CW, FLEXNER C, MCFARLAND RT et al.: Pharmacokinetics and safety of AMD3100, a novel antagonist of the CXCR4 chemokine receptor in human volunteers. Antimicrob. Agents Chemother. (2000) 44:1667-1673.
28. LIU R, PAXTON WA, CHOE S et al: Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell (1996) 86:367-377.
29. TRKOLA A, KETAS TJ, NAGASHIMA KA et al.: Potent, broad-spectrum inhibition of human immunodeficiency virus type 1 by the CCR5 monoclonal antibody PRO 140. J. Virol. (2001) 75:579-588.
30. BABA M, NISHIMURA O, KANZAKI N et al.: A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity. Proc. Natl. Acad. Sci. USA (1999) 96:5698-5703. The first report of a small molecule CCR5 antagonists.
31. HALE JJ, BUDHU RJ, MILLS SG et al.: 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 1: discovery of the pyrrolidine scaffold and determination of its stereochemical requirements. Bioorg. Med. Chem. Lett. (2001) 11:1437-1440.
32. HALE JJ, BUDHU RJ, HOLSON EB et al.: 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 2: lead optimization affording selective, orally bioavailable compounds with potent anti-HIV activity. Bioorg. Med. Chem. Lett. (2001) 11:2741-2745.
33. KAZMIERSKI W, BIFULCO N, YANG H et al.: Recent progress in discovery of small-molecule CCR5 chemokine receptor ligands as HIV-1 inhibitors. Bioorg. Med. Chem. (2003) 11:2663-2676. A comprehensive review of small molecule CCR5 inhibitors.
34. BOYLE CD, PALANI A: Structure activity relationship studies: M2 and CCR5 receptor antagonists. Curr. top. med. chem. (2003) 3:1155-1169.
35. STRIZKI JM, XU S, WAGNER NE et al.: SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo. Proc. Natl. Acad. Sci. USA (2001) 98:12718-12723.
36. MAEDA K, YOSHIMURA K, SHIBAYAMA S et al.: Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5 HIV-1 infection through their antagonistic effects on CCR5. J. Biol. Chem. (2001) 276:35194-35200.
37. ZOU YR, KOTTMANN AH, KURODA M, TANIUCHI I, LITTMAN DR: Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature (1998) 393:595-599.
38. KUHMANN SE, PUGACH P, KUNSTMAN KJ et al.: Genetic and phenotypic analyses of human immunodeficiency virus type 1 escape from a small-molecule CCR5 inhibitor. J. Virol. (2004) 78:2790-2807.