产品说明书

Rilpivirine

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Chemical Structure| 500287-72-9 同义名 : R278474;TMC278;DB08864
CAS号 : 500287-72-9
货号 : A112484
分子式 : C22H18N6
纯度 : 98%
分子量 : 366.42
MDL号 : MFCD11046372
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(136.46 mM)，配合低频超声助溶，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 Rilpivirine is a diarylpyrimidine derivative that functions as a non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV-1 infection. It demonstrated more pronounced activity against wild-type HIV-1 (EC50 = 0.4 nM) and all single and double mutants as compared to other NNRTIs, such as nevirapine, efavirenz, TMC120, and TMC125. Rilpivirine at 1 μM showed no sign of virus breakthrough for wild-type HIV-1 within 30 days. Compared to the E-isomer of rilpivirine, the Z-isomer exhibited relatively high potency against wild-type HIV-1 with an EC50 value of 0.6 nM, but showed five times less activity against single and double mutants. Rilpivirine inhibited 81% of the 1200 recombinant clinical isolates collected from HIV-infected patients with an EC50 value less than 1 nM. The IC50 values of rilpivirine for the inhibition of CYP450 isoforms 3A4, 2C9, and 2D6 were 4.6, 5.0, and >10 μM, respectively. The pharmacokinetic studies after the i.v. administration of rilpivirine showed that the elimination half-life was 4.4 h in rat and 31h in dog. The exposure (AUCinf) were 3.1 μg h/mL (i.v. dose of 4 mg/kg) in rat, 8.7 μg h/mL (i.v. dose of 1.25 mg/kg) in dog, 1.4 μg h/mL (i.v. dose of 1.25 mg/kg) in monkey, and 44 μg h/mL (i.v. dose of 1.25 mg/kg) in rabbit.
作用机制 Rilpivirine is a NNRTI that shows potent activity against wild-type and mutant HIV-1 strains. The improved activity in comparison to other NNRTIs may involve a specific interaction of the cyano group in wing I with the indole ring of Trp229.
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human MT4 cells Function assay 72 h Antiviral activity against NNRTI-resistant HIV1 harboring reverse transcriptase Y188L mutant infected in human MT4 cells assessed as inhibition of viral replication after 72 hrs by HeLa-CD4-LTR-beta-gal assay, EC50=0.0037 μM 23137340
human PBMC cells Function assay Antiviral activity against Human immunodeficiency virus 1 subtype D isolate 92UG001 infected in human PBMC cells by cell based assay, EC50=0.00026 μM 19933797
human TZM-bl cells Cytotoxicity assay 4 days Cytotoxicity against human TZM-bl cells after 4 days by XTT assay, CC50=19.4 μM 22856541
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
NCT02491242 - Completed - Spain ... 展开 >> Ramon y Cajal Hospital Madrid, Spain, 28034 收起 <<
NCT02605954 HIV-1 Infection Phase 3 Completed - -
NCT03631732 HIV-1 Infection Phase 3 Recruiting August 2020 -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.73mL

0.55mL

0.27mL

13.65mL

2.73mL

1.36mL

27.29mL

5.46mL

2.73mL
参考文献

[1]Azijn H, Tirry I, et al. TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. Antimicrob Agents Chemother. 2010 Feb;54(2):718-27.

[2]Janssen PA, Lewi PJ, et al. In search of a novel anti-HIV drug: multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl] -2,6-dimethylphenyl] amino] -2-pyrimidinyl] amino] benzonitrile (R278474, rilpivirine). J Med Chem. 2005 Mar 24;48(6):1901-9.