GSK3739936 (BMS-986180) 是一种有效的 HIV-1 变构整合酶 (HIV-1 allosteric integrase) 抑制剂，IC50为 11.1 nM，EC50为 1.7 nM。GSK3739936 也是一种弱CYP抑制剂 (IC50>24.3 μM)。GSK3739936 在实验动物中表现出良好的药代动力学特性，吸收快、清除率低至中等，以及口服生物利用度良好。
| 生物活性 | GSK3739936 (BMS-986180) is a potentHIV-1allosteric integraseinhibitor with anIC50value of 11.1 nM and anEC50value of 1.7 nM. GSK3739936 is also a weak CYP inhibitor (IC50>24.3 μM). GSK3739936 shows favorable pharmacokinetic property in preclinical species with rapid absorption, low to moderate clearance and excellent oral bioavailability[1]. |
| IC50& Target | IC50: 11.1 nM (HIV-1 integrase)[1]
EC50: 1.7 nM (HIV-1 integrase)[1]
IC50: >24.3 μM (CYP)[1] |
体外研究
(In Vitro) | GSK3739936 is not cytotoxic to MT-2 cells, exhibiting CC50values of >20 μM[1].
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体内研究
(In Vivo) | GSK3739936 exhibits favorable pharmacokinetic property with rapid absorption, low to moderate clearance and excellent oral bioavailability[1].
Pharmacokinetic Parameters of GSK3739936 in Preclinical Species[1].
| Male CD-1 mice | Male Sprague-Dawley rats | Cynomolgus monkey | Male beagle dogs | | IV dose (mg/kg) | 1 | 1 | 1 | 1 | | CL (mL/min/kg) | 5.4 | 5.5 | 14.5 | 2.9 | | t1/2(h) | 6.3 | 4.3 | 2.4 | 5.1 | | Vss(L/kg) | 2.4 | 1.8 | 1.5 | 0.7 | | PO dose (mg/kg) | 5 | 5 | 2 | 2 | | Cmax(nM) | 2361 | 2762 | 525 | 2963 | | tmax(h) | 5 | 2.7 | 2 | 2 | | AUC (nM·h) | 24516 | 14022 | 2231 | 18471 | | F (%) | 89 | 52 | 54 | 75 |
| Animal Model: | Male CD-1 mice, male Sprague-Dawley rats, cynomolgus monkey and male beagle dogs[1] | | Dosage: | 1 mg/kg for IV; 5 or 2 mg/kg for PO | | Administration: | PO or IV; single dosage | | Result: | Exhibited a low clearance in the mouse, rat, and dog with moderate to long elimination half-lives, while displays moderate clearance and a short elimination half-life in the cynomolgus monkey.
The absolute oral bioavailability ranged between 52 and 89%.
The tmaxvalue of 2-5 h suggesting rapid absorption in all four species. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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