"目錄號: HY-14266
Dapivirine(TMC 120, TMC 120 R147681)是HIV非核苷逆轉(zhuǎn)錄酶抑制劑（NNRTI），IC50為24 nM，能抑制包括NNRTI抗性的各種HIV-1毒株。
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生物活性
Description
Dapivirine(TMC 120, TMC 120 R147681) is a NNRTI for HIV reverse transcriptase with IC50 of 24 nM, inhibits a broad panel of HIV-1 isolates from different classes, inclucing a wide range of NNRTI-resistant isolates.IC50 value: 24 nM [1]Target: HIV reverse transcriptase; NNRTIsin vitro: TMC120-R147681 is a diarylpyrimidine with high activity against wild-type and mutant HIV. A 24-h treatment with 1,000 nM UC-781 or 100 nM TMC120-R147681 prevented cell-free HIV infection, whereas 10-fold-higher concentrations blocked cell-associated HIV, TMC120-R147681 apparently blocked infection in the primary cultures at a 10 nM concentration, but secondary cultures revealed that a 100 nM concentration was needed to completely prevent proviral integration [1]. Dapivirine is well tolerated by epithelial cells, T cells, macrophages, and cervical tissue explants with CC50 (50% cytotoxic concentration) of 10 μM to 20 μM. Dapivirine potently inhibits infection by both X4- and R5-utilizing HIV-1 strains with IC50 of 1.46 nM in cell-based assays. Dapivirine potently inhibits HIV-1BaL infection of human ectocervical explant tissue in a dose-dependent manner, as evaluated by the reduction in both p24 release and provirus content in cultured explants. Dapivirine inhibits the transmission of virus to permissive T cells in a dose-dependent manner, with an IC50 of 0.1 nM. Dapivirine results in significant inhibition of HIV infection when explants are challenged with virus immediately with IC90 of 100 nM. Dapivirine is also able to inhibit viral dissemination by migratory cells [2].in vivo: Dapivirine-containing gel at vaginal level inhibits cell-associated HIV infection in mice [3]. More placebo (7 of 12) than Dapivirine (3 of 24) gel users has positive vaginal swab results, with white blood cells being the most common finding. Dapivirine (0.05%) results in Cmax of 715 pg/mL, AUC of 15 ng×h/mL and T1/2 of 89.87 hours in plasma after 14 days post-dose. Mean Dapivirine (0.05%) concentrations in vaginal fluids collected at the introitus, mid vagina, and cervix are in the range of 62-265 μg/g on day 1 [4].
Clinical Trial
International Partnership for Microbicides, Inc.
Human Immunodeficiency Virus
February 2015
Phase 1
International Partnership for Microbicides, Inc.-National Institute of Allergy and Infectious Diseases (NIAID)
Human Immunodeficiency Virus
December 2013
Phase 2
International Partnership for Microbicides, Inc.
HIV
December 2012
Phase 1
International Partnership for Microbicides, Inc.
HIV Prevention
August 2016
Phase 3
International Partnership for Microbicides, Inc.
HIV-1 Infections
June 2009
Phase 1-Phase 2
International Partnership for Microbicides, Inc.
HIV 1 Infection
September 29, 2015
Phase 1
International Partnership for Microbicides, Inc.
HIV Infections
August 2009
Phase 1
International Partnership for Microbicides, Inc.
HIV- Prevention
September 1, 2015
Phase 1
International Partnership for Microbicides, Inc.
Pharmaokinetics
September 2013
Phase 1
International Partnership for Microbicides, Inc.
Topical Penile Exposures
March 2011
Phase 1
International Partnership for Microbicides, Inc.-Tibotec Pharmaceutical Limited
HIV Infections
October 2004
Phase 1
International Partnership for Microbicides, Inc.
HIV Infections
April 2010
Phase 1-Phase 2
International Partnership for Microbicides, Inc.
HIV Infections
July 2011
Phase 3
International Partnership for Microbicides, Inc.
HIV Infections
July 2011
Phase 3
International Partnership for Microbicides, Inc.
Pharmacokinetics
November 2013
Phase 1
International Partnership for Microbicides, Inc.
HIV Infections
January 2011
Phase 1
International Partnership for Microbicides, Inc.
HIV Infections
November 2005
Phase 1
International Partnership for Microbicides, Inc.-Microbicide Trials Network-National Institutes of Health (NIH)
Human Immunodeficiency Virus
March 2014
Phase 2
International Partnership for Microbicides, Inc.
HIV Infections-Acquired Immunodeficiency Syndrome-Healthy
July 2009
Phase 1-Phase 2
International Partnership for Microbicides, Inc.-Tibotec Pharmaceutical Limited
HIV Infections
July 2005
Phase 1
International Partnership for Microbicides, Inc.
HIV Infections-Acquired Immunodeficiency Syndrome
November 2009
Phase 1-Phase 2
International Partnership for Microbicides, Inc.
HIV Infections
April 2010
Phase 1
International Partnership for Microbicides, Inc.
HIV Infections
November 2011
Phase 1
International Partnership for Microbicides, Inc.
Human Immunodeficiency Virus
August 2016
Phase 3
International Partnership for Microbicides, Inc.
HIV
January 2015
Phase 1
International Partnership for Microbicides, Inc.
HIV Infections
November 2007
Phase 1
International Partnership for Microbicides, Inc.-National Institute of Allergy and Infectious Diseases (NIAID)
HIV Infections
June 2012
Phase 3
International Partnership for Microbicides, Inc.
HIV Infections
May 2007
Phase 1
International Partnership for Microbicides, Inc.
HIV Infections
August 2012
Phase 1
International Partnership for Microbicides, Inc.
HIV Infections-HIV-1
December 2005
Phase 1-Phase 2
International Partnership for Microbicides, Inc.
HIV Infections
Phase 1-Phase 2
International Partnership for Microbicides, Inc.
HIV Infections
October 2005
Phase 1-Phase 2
International Partnership for Microbicides, Inc.-Gilead Sciences
HIV-1-infection
November 2017
Phase 2
International Partnership for Microbicides, Inc.
Human Immunodeficiency Virus
February 2013
Phase 2
International Partnership for Microbicides, Inc.
Human Immunodeficiency Virus
August 2013
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