Advanced search
Publication Cover
Expert Opinion on Investigational Drugs Volume 14, 2005 - Issue 6
Submit an article Journal homepage
105
Views
41
CrossRef citations to date
0
Altmetric
Review

The discovery of a class of novel HIV-1 maturation inhibitors and their potential in the therapy of HIV

Donglei Yu Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA. [email protected]
,
Carl T Wild V. I. Technologies (formerly Panacos Pharmaceuticals), 209 Perry Parkway, Gaithersburg, MD 20878, USA
,
David E Martin Medical Center, Box 2926, SORF, Duke University, Durham, NC 27710, USA
,
Susan L Morris-Natschke Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA. [email protected]
,
Chin-Ho Chen V. I. Technologies (formerly Panacos Pharmaceuticals), 209 Perry Parkway, Gaithersburg, MD 20878, USA
,
Graham P Allaway Medical Center, Box 2926, SORF, Duke University, Durham, NC 27710, USA
&
Kuo-Hsiung Lee Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA. [email protected]
 show all
Pages 681-693 | Published online: 11 Jul 2005

Bibliography

  • PANT A, LOT AG, MURA M, MARCEDDU T, LA COLLA P, MARONGIU ME: Targeting HIV: old and new players. Curr. Drug Targets Infect. Disord. (2002) 2:17–32.
  • MILLER MD, HAZUDA DJ: New antiretroviral agents: looking beyond protease and reverse transcriptase. Curr. Opin. Microbial. (2001) 4:535–539.
  • MOORE JP, STEVENSON M: New targets for inhibitors of HIV-1 replication. Nat. Rev Mot. Cell Biol. (2000) 1:40–49.
  • FUNG HB, GUO Y: Enfuvirtide: a fusion inhibitor for the treatment of HIV infection. Clin. Ther. (2004) 26:352–378.
  • STEPHENSON J: The art of HAART':researchers probe the potential and limits of aggressive HIV treatments. JAMA (1997) 277:614–616.
  • KLEIN MB, WILLEMOT P, MURPHY T, LALONDE RG: The impact of initial highly active antiretroviral therapy on future treatment sequences in HIV infection. AIDS (2004) 18:1895–1904.
  • LUCAS GM, CHAISSON RE, MOORE RD: Highly active antiretroviral therapy in a large urban clinic: risk factors for virologic failure and adverse drug reactions. Ann. Intern. Med. (1999) 131:81–87.
  • LEE K-H: Current developments in the discovery and design of new drug candidates from plant natural product leads. J. Nat. Prod (2004) 67:273–283.
  • •A review of natural products as leads in drug discovery.
  • CONNOLLY JD, HILL RA: Triterpenoids. Nat. Prod Rep. (2001) 18:560–578.
  • HUANG L, CHEN CH: Molecular targets of anti-HIV-1 triterpenes. Curt: Drug Targets Infect. Disord. (2002) 2:33–36.
  • •A review of anti-HIV-1 triterpenes with different mechanisms of action.
  • DE CLERCQ E: Current lead natural products for the chemotherapy of human immunodeficiency virus (HIV) infection. Med. Res. Rev. (2000) 20:323–349.
  • •A review of natural products as leads in anti-HIV drug discovery.
  • HIRABAYASHI K, IWATA S, MATSUMOTO H et al: Antiviral activities of glycyrrhizin and its modified compounds against human immunodeficiency virus Type 1 (HIV-1) and herpes simplex virus Expert Op/n. lnvestig. Drugs (2005) 14(6)691Type 1 (HSV-1) in vitro. Chem. Pharm. Bull. (1991) 39:112–115.
  • MAYAUX JF, BOUSSEAU A, PAUWELS R et al.: Triterpene derivatives that block entry of human immunodeficiency virus Type 1 into cells. Proc. Natl. Acad. Sci. USA (1994) 91:3564–3568.
  • SOLER F, POUJADE C, EVERS Metal.:Betulinic acid derivatives: a new class of specific inhibitors of human immunodeficiency virus type 1 entry. J. Med. Chem. (1996) 39:1069–1083.
  • •Discovery of RPR-103116 through structural modification of betulinic acid.
  • HOLZ-SMITH SL, SUN IC, JIN L, MATTHEWS TJ, LEE KH, CHEN CH: Role of human immunodeficiency virus (HIV) Type 1 envelope in the anti-HIV activity of the betulinic acid derivative IC-9564. Antimicrob. Agents Chemother. (2001) 45:60–66.
  • YUAN X, HUANG L, HOP, LABRANCHE C, CHEN CH: Conformation of gp120 determines the sensitivity of HIV-1 DH012 to the entry inhibitor IC-9564. Virology (2004) 324:525–530.
  • SAHU NP: Triterpenoid saponins of Mimusops elengi Phytochemistry (1996) 41:883–886.
  • EL-MEKKAWY S, MESELHY MR, NAKAMURA N et al.: Anti-HIV-1 and anti-HIV-1-protease substances from Ganoderma lucidum. Phytochemistry (1998) 49: 1651-1657.
  • XU H-X, MING D-S, DONG H, BUT PP-H: A new anti-HIV triterpene from Geumjaponicum. Chem. Pharm. Bull. (2000) 48:1367–1369.
  • EVERS M, POUJADE C, SOLER F et al:Betulinic acid derivatives: a new class of human immunodeficiency virus type-1-specific inhibitors with a new mode of action. ./. Med. Chem. (1996) 39:1056–1068.
  • •An informative study of the structural modification of betulinic acid.
  • KASHIWADA Y, HASHIMOTO F, COSENTINO LM, CHEN C-H, GARRETT PE, LEE K-H: Betulinic acid and dihydrobetulinic acid derivatives as potent anti-HIV agents. j Med. Chem. (1996) 39:1016–1017.
  • ••The discovery of DSB as a potent anti-HIV-1 agent.
  • KANAMOTO T, KASHIWADA Y, KANBARA K et al.: Anti-human immunodeficiency virus activity of YK-FH312 (a betulinic acid derivative), a novel compound blocking viral maturation. Antimicrob. Agents Chemother. (2001) 45:1225–1230.
  • •The first report of the inhibition of DSB during maturation.
  • LI F, GOILA-GAUR R, SALZWEDEL K et al: PA-457: A potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing. Proc. Natl. Acad. Sci. USA (2003) 100:13555–13560.
  • •The first study that revealed the unique mode of action of DSB at the CA-SP1 Junction.
  • FUJIOKA T, KASHIWADA Y, KILKUSKIE RE et al: Anti-AIDS agents, 11. Betulinic acid and platanic acid as anti-HIV principles from Syzigium clavillorum, and the anti-HIV activity of structurally related triterpenoids. Nat. Prod. (1994) 57:243–247.
  • •Lead generation with betulinic acid as a potent anti-HIV agent.
  • HASHIMOTO F, KASHIWADA Y, COSENTINO LM, CHEN C-H, GARRETT PE, LEE K-H: Anti-AIDS agents 27. Synthesis and anti-HIV activity of betulinic acid and dihydrobetulinic acid derivatives. Bioorg. Med. Chem. (1997) 5:2133–2143.
  • •The detailed report of a modification and SAR study of betulinic acid as a potent anti-HIV-1 agent.
  • KASHIWADA Y, WANG HK, NAGAO T et al: Anti-AIDS agents. 30. Anti-HIV activity of oleanolic acid, pomolic acid, and structurally related triterpenoids. Nat. Prod. (1998) 61:1090–1095.
  • CICHEWICZ RH, KOUZI SA: Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. Med. Re.c. Rev. (2003) 24:90–114.
  • SINGH SS, PATRO B, TRIPATHI V, SRIVASTAVA A, PANDEY SC, GHOSH AC: Betulinic acid and its pharmacological activity - a review. J. Med. Aromatic Plant Sci. (2002) 24:1031–1037.
  • YUN Y, HAN S, PARK E et aL: Immunomodulatory activity of betulinic acid by producing pro-inflammatory cytokines and activation of macrophages. Arch. Pharm. Res. (2003) 26:1087–1095.
  • LABROSSE B, TREBOUTE C, ALIZON M: Sensitivity to a nonpeptidic compound (RPR-103611) blocking human immunodeficiency virus type 1 Env-mediated fusion depends on sequence and accessibility of the gp41 loop region. Virol. (2000) 74:2142–2150.
  • LABROSSE B, PLESKOFF 0, SQL N, JONES C, HENIN Y, ALIZON M: Resistance to a drug blocking human immunodeficiency virus Type 1 entry (RPR103611) is conferred by mutations in gp4i.j Virol. (1997) 71:8230–8236.
  • DUMONCEAUX J, CHANEL C, VALENTE S, QUIVET L, BRIAND P, HAZAN U: Mutations in the env gene of human immunodeficiency virus Type 1 NDK isolates and the use of African green monkey CXCR4 as a co-receptor in COS-7 cells. J. Gen. Virol. (1999)80\(Part 8):1975–1982.
  • KASHIWADA Y, HASHIMOTO F, COSENTINO LM, CHEN CH, GARRETT PE, LEE KH: Betulinic acid and dihydrobetulinic acid derivatives as potent anti-HIV agents. J. Med. Chem. (1996) 39:1016–1017.
  • SUN IC, KASHIWADA Y, MORRIS-NATSCHKE SL, LEE KH: Plant-derived terpenoids and analogues as anti-HIV agents. Curr. Top. Med. Chem. (2003) 3:155–169.
  • ••A useful review of anti-HIV terpenoids andtheir analogues.
  • WANG BH, POLYA GM: Selective inhibition of cyclic AMP-dependent protein kinase by amphiphilic triterpenoids and related compounds. Phytochemistry (1996) 41:55–63.
  • RECIO MC, GINER RM, MANEZ S et al.: Investigations on the steroidal anti-inflammatory activity of triterpenoids from Diospyros leucomelas. Planta Med. (1995) 61:9–12.
  • SUN IC, WANG HK, KASHIWADA Y et al.: Anti-AIDS agents. 34. Synthesis and structure-activity relationships of betulin derivatives as anti-HIV agents. J. Med. Chem. (1998) 41:4648–4657.
  • •A detailed report of modification and SAR study of betulin as a potent anti-HIV-1 agent.
  • CANNON J: Analog design. In: Burger's Medicinal Chemistry and Drug Discovery, Wolff M (Ed.) John Wiley & Sons, Inc., New York, USA (1994):783.
  • •A report of 3-0-amido-betulinic acid analogues.
  • KASHIWADA Y, CHIYO J, IKESHIRO Y et al.: Synthesis and anti-HIV activity of 3-alkylamido-3-deoxy-betulinic acid derivatives. Chem. Pharm. Bull. (2000) 48:1387–1390.
  • RAMBAUT A, POSADA D, CRANDALL KA, HOLMES EC: The causes and consequences of HIV evolution. Nat. Rev. Genet. (2004) 5:52–61.
  • ZHOU J, YUAN X, DISMUKE D et al: Small-molecule inhibition of human immunodeficiency virus Type 1 replication by specific targeting of the final step of virion maturation. J. Vim]. (2004) 78:922–929.
  • •A discussion of the effects of the L363F mutation in the CA-SP 1 junction.
  • SWANSTROM R, WILLS JW: Synthesis, assembly, and processing of viral proteins. Retroviruses (1997):263–334.
  • FREED EO: HIV-1 gag proteins: diverse functions in the virus life cycle. Virology (1998) 251:1–15.
  • VOGT VM: Proteolytic processing and particle maturation. Curr. Top. Microbial. Lnmunol. (1996) 214:95–131.
  • KRAUSSLICH HG, SCHNEIDER H, ZYBARTH G, CARTER CA, WIMMER E: Processing of in vitro-synthesized gagprecursor proteins of human immunodeficiency virus (HIV) Type 1 by HIV proteinase generated in Echerichia coli J. Virzi]. (1988) 62:4393–4397.
  • MERVIS RJ, AHMAD N, LILLEHOJ EP et al.: The gag gene products of human immunodeficiency virus Type 1: alignment within the gag open reading frame, identification of posttranslational modifications, and evidence for alternative gag precursors. J. Vim]. (1988) 62:3993–4002.
  • ERICKSON-VIITANEN S, MANFREDI J, VIITANEN P et al: Cleavage of HIV-1 gag polyprotein synthesized in vitro: sequential cleavage by the viral protease. AIDS Res. Hum. Retroviruses (1989) 5:577–591.
  • KAPLAN AH, ZACK JA, KNIGGE M et al.: Partial inhibition of the human immunodeficiency virus type 1 protease results in aberrant virus assembly and the formation of noninfectious particles. Virol (1993) 67:4050–4055.
  • SALZWEDEL K, GOILA-GAUR R, LI F et al.: Selection for and characterization of HIV-1 isolates resistant to the maturation inhibitor PA-457. The 15th International AIDS Conference, Bangkok, Thailand (2004).
  • ZHOU J, CHEN CH, AIKEN C: The sequence of the CA-SP1 junction accounts for the differential sensitivity of HIV-1 and SIV to the small molecule maturation inhibitor 3-0-(3',3'-dimethylsucciny9-betulinic acid. Retrovirology (2004) 1:15.
  • •An additional investigation of HIV-1 and SIV mutation at the CA-SP1 junction.
  • NAMIKAWA R, WEILBAECHER KN, KANESHIMA H, YEE EJ, McCUNE JM: Long-term human hematopoiesis in the SCID-hu mouse. I Exp. Med. (1990) 172:1055–1063.
  • RABIN L, HINCENBERGS M, MORENO MB et al: Use of standardized SCID-hu Thy/Liv mouse model for preclinical efficacy testing of anti-human immunodeficiency virus Type 1 compounds. Antimicrob. Agents Chemother. (1996) 40:755–762.
  • ALLAWAY G, BARE J, KILGORE N et al:The first-in-class maturation inhibitor, PA-457, is a potent inhibitor of HIV replication both in vitro and in vivo. The 25th International AIDS Conference, Bangkok, Thailand (2004).
  • MARTIN D, SMITH P, WILD C, ALLAWAY G: LI vitro and in vivo disposition of PA-457, a novel inhibitor of HIV-1 maturation. The 15th International AIDS Conference, Bangkok, Thailand (2004).
  • MARTIN D, BALLOW C, DOTO J, BLUM R, WILD C, ALLAWAY G: The safety, tolerability, and pharmacokinetics of multiple oral doses of PA-457, the first-in-class HIV maturation inhibitor, in healthy volunteers. The 12th Conference on Retroviruses and Opportunistic Infections, MA, USA (2005).
  • MARTIN D, JACOBSON J, SCHURMANN D et al: PA-457, the first-in-class maturation inhibitor, exhibits antiviral activity following a single oral dose in HIV-1-infected patients. The 12th Conference on Retroviruses and Opportunistic Infections, MA, USA (2005).
  • BARDITCH-CROVO P, DEEKS SG, COLLIER A et al: Phase I/II trial of the pharmacokinetics, safety, and antiretroviral activity of tenofovir disoproxil fumarate in human immunodeficiency virus-infected adults. Antimicrob. Agents Chemother. (2001) 45:2733–2739.
  • RICHMAN D, BOZZETTE S, MORTON S et al: The prevalence of antiretroviral drug resistance in the US. 41st Interscience Conference on Antimicrobrobial Agents Chemotherapy, IL, USA (2001).
  • LABONTE J, LEBBOS J, KIRKPATRICK P: Enfuvirtide. Nat. Rev Drug Discov. (2003) 2:345–346.
  • SUN IC, SHEN JK, WANG HK, COSENTINO LM, LEE KH: Anti-AIDS agents. 32. Synthesis and anti-HIV activity of betulin derivatives. Bioorg. Med. Chem. Lett. (1998) 8:1267–1272.

Websites

  • http://www.aidsinfo.nih.govidrugs/ For current information on approved and experimental anti-HIV agents.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.