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Dapivirine

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Chemical Structure| 244767-67-7 同义名 : 达匹维林 ;TMC120;R147681
CAS号 : 244767-67-7
货号 : A175194
分子式 : C20H19N5
纯度 : 98%
分子量 : 329.398
MDL号 : MFCD09833899
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 45 mg/mL(136.61 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
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 ... 展开 >> California Family Health Council Berkeley, California, United States, 94710 California Family Health Council Los Angeles, California, United States, 90010 收起 <<
NCT03537092 Safety of Vaginal Film Use Phase 1 Recruiting January 2019 United States, Pennsylvania ... 展开 >> Magee womens Hospital of UPMC Recruiting Pittsburgh, Pennsylvania, United States, 15213 Contact: Ingrid Macio, PA-C 收起 <<
NCT03648931 - Recruiting September 2018 Malawi ... 展开 >> 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 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.04mL

0.61mL

0.30mL

15.18mL

3.04mL

1.52mL

30.36mL

6.07mL

3.04mL
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