For research use only. Not for use in humans.
Molecular Weight(MW): 329.4
Dapivirine (TMC120) is a non-nucleoside inhibitor 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. Phase 3.
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|Description||Dapivirine (TMC120) is a non-nucleoside inhibitor 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. Phase 3.|
Dapivirine prevents HIV-induced syncytium formation in the nanomolar range and shows a low cytostatic activity. Dapivirine apparently blocks HIV-1 infection in the primary cultures at a 10 nM concentration, but secondary cultures reveals that a 100 nM concentration is needed to completely prevent proviral integration.  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. 
|In vivo||Dapivirine-containing gel at vaginal level inhibits cell-associated HIV infection in mice.  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. |
|In vitro||DMSO||34 mg/mL (103.21 mM)|
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Clinical Trial Information
|NCT Number||Recruitment||interventions||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT03593655||Recruiting||Device: Dapivirine vaginal ring|Drug: FTC/TDF||HIV Infections||National Institute of Allergy and Infectious Diseases (NIAID)||January 14 2019||Phase 2|
|NCT03393468||Completed||Drug: Dapivirine gel||HIV Infections||National Institute of Allergy and Infectious Diseases (NIAID)||May 31 2018||Phase 1|
|NCT03239483||Completed||Drug: Dapivirine gel|Drug: Placebo gel||HIV Infections||National Institute of Allergy and Infectious Diseases (NIAID)||October 26 2017||Phase 1|
|NCT02858037||Completed||Combination Product: Dapivirine Vaginal Ring||Human Immunodeficiency Virus||International Partnership for Microbicides Inc.||August 2016||Phase 3|
|NCT02862171||Completed||Drug: Dapivirine Vaginal Ring-004||HIV Prevention||International Partnership for Microbicides Inc.||July 13 2016||Phase 3|
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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