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XM323, a novel non-peptidyl inhibitor of HIV protease with potent in vitro antiviral activity.

Otto MJ, Reid CD, Garber S, Winslow D, Scarnati H, Lam P; International Conference on AIDS.

Int Conf AIDS. 1993 Jun 6-11; 9: 34 (abstract no. WS-A18-3).

Du Pont Merck Pharmaceutical Company, Glenolden, PA.

OBJECTIVE: Currently the most potent inhibitors of HIV protease are peptidyl in nature. Our objective was to use the crystallographic structural information of HIV-1 protease to design and synthesize novel non-peptidyl inhibitors of the enzyme and to determine their antiviral activity in vitro. METHOD: The antiviral activity of test compounds was determined by yield reduction assays in MT-2, H9 and peripheral blood mononuclear cells. The yield of virus was measured by p24 and by plaque assays and the 90% inhibitory concentrations, IC90s, were calculated from dose response curves. RESULTS: XM323, a representative of a new class of non-peptidyl inhibitors, was identified as a potent inhibitor of HIV-1 and HIV-2 replication in vitro. The compound was equally effective against laboratory strains of HIV-1 and HIV-2 and against AZT sensitive and resistant clinical isolates of HIV-1 with a mean IC90 against all viruses tested of 0.14 +/- 0.06 microM. XM323 was well tolerated by MT-2 and PBM cells in culture with an in vitro therapeutic index of > or = 760. CONCLUSION: XM323 is a potent inhibitor of HIV replication in vitro and represents a new class of de novo designed non-peptidyl inhibitors of HIV-1 protease.

Publication Types:
  • Meeting Abstracts
  • Acquired Immunodeficiency Syndrome
  • Antiviral Agents
  • HIV
  • HIV Core Protein p24
  • HIV Protease
  • HIV-1
  • HIV-2
  • In Vitro
  • Zidovudine
  • immunology
  • reverse transcriptase, Human immunodeficiency virus 1
Other ID:
  • 93334760
UI: 102204134

From Meeting Abstracts

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