生物活性

• 靶点	Reverse Transcriptase IC50:24nM

• 描述Dapivirine (TMC120), the prototype of diarylpyrimidines (DAPY), is an orally active and nonnucleoside reverse transcriptase inhibitor (NRTI). Dapivirine (4-64 μM, 24, 48, 72, 96 and 120 hours) inhibits proliferation of glioma cells and induces apoptosis (16 μM, 12-48 h). Dapivirine (8 and 16 μM, 12 h) enhances invasion of glioma cells. Dapivirine (16 μM, 12 h, 24 h and 48 h) promotes autophagy in U87 cells^[3]. Dapivirine apparently blocks 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^[4]. 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^[5].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01755741	Human Immunodeficiency Virus	Phase 1	Completed	-	United States, California ... more >> California Family Health Council Berkeley, California, United States, 94710 California Family Health Council Los Angeles, California, United States, 90010 Collapse <<
  NCT03537092	Safety of Vaginal Film Use	Phase 1	Recruiting	January 2019	United States, Pennsylvania ... more >> Magee womens Hospital of UPMC Recruiting Pittsburgh, Pennsylvania, United States, 15213 Contact: Ingrid Macio, PA-C Collapse <<
  NCT03648931	-	-	Recruiting	September 2018	Malawi ... more >> Blantyre Clinical Research Site Recruiting Blantyre, Malawi Contact: Frank Taulo, MBBS, MPH, FCOG          Contact       ftaulo@yahoo.com    South Africa Wits Reproductive Health and HIV Institute (WRHI) Clinical Research Site Recruiting Johannesburg, South Africa Contact: Thesla Palanee-Phillips, PhD, MMedSci, MSc          Contact       tpalanee@whri.ac.za    Uganda Makerere University - Johns Hopkins University (MU-JHU) Research Collaboration Clinical Research Site Recruiting Kampala, Uganda Contact: Juliane Etima, BSc, MA Psy          Contact       jetima@mujhu.org    Zimbabwe Zengeza Clinical Research Site Recruiting Harare, Zimbabwe Contact: Petina Musara, BSW          Contact       pmusara@uzchs-ctu.org Collapse <<

• 更多
• 参考文献

• [1] Van Herrewege Y, Michiels J, et al. In vitro evaluation of nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 as human immunodeficiency virus microbicides. Antimicrob Agents Chemother. 2004 Jan;48(1):337-9.

  [2] Di Fabio S, Van Roey J, et al. Inhibition of vaginal transmission of HIV-1 in hu-SCID mice by the non-nucleoside reverse transcriptase inhibitor TMC120 in a gel formulation. AIDS. 2003 Jul 25;17(11):1597-604.

  [3] Liu W, Song XL, Zhao SC, He M, Wang H, Chen Z, Xiang W, Yi G, Qi S, Liu Y. Antitumor Activity and Mechanism of a Reverse Transcriptase Inhibitor, Dapivirine, in Glioblastoma. J Cancer. 2018 Jan 1;9(1):117-128

  [4] Van Herrewege Y, Michiels J, Van Roey J, Fransen K, Kestens L, Balzarini J, Lewi P, Vanham G, Janssen P. In vitro evaluation of nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 as human immunodeficiency virus microbicides. Antimicrob Agents Chemother. 2004 Jan;48(1):337-9

  [5] Fletcher P, Harman S, Azijn H, Armanasco N, Manlow P, Perumal D, de Bethune MP, Nuttall J, Romano J, Shattock R. Inhibition of human immunodeficiency virus type 1 infection by the candidate microbicide dapivirine, a nonnucleoside reverse transcriptase inhibitor. Antimicrob Agents Chemother. 2009 Feb;53(2):487-95

• 更多

• Collapse