Dolutegravir | CAS:1051375-16-6

Chemscene社は、高品質な低分子化合物を提供しているメーカーです。
Chemscene社のDolutegravir(CAS:1051375-16-6)をご紹介します。

※本製品は研究用です。研究用以外には使用できません。

Name:Dolutegravir; S/GSK1349572; GSK1349572
Cat. No. :CS-0454
CAS No. :1051375-16-6
Formula:C20H19F2N3O5
M. Wt. : 419.38
Solubility:DMSO: 10 mg/mL

Dolutegravir is an inhibitor of HIV-1 integrase-catalyzed strand transfer with IC50 of 2.7 nM.IC50 & Target: IC50: 2.7 nM (HIV-1 integrase)[1]In Vitro: The EC50 of Dolutegravir (S/GSK1349572) against HIV-1 is 0.51 nM in PBMCs, 0.71 nM in MT-4 cells, and 2.2 nM in the PHIV assay, which uses a pseudotyped self-inactivating virus. The 50% cytotoxic concentrations (CC50) for Dolutegravir in proliferating IM-9, U-937, MT-4, and Molt-4 cells are 4.8, 7.0, 14, and 15 μM, respectively. In unstimulated and stimulated PBMCs, the CC50 are 189 μM and 52 μM, respectively. Based on the EC50 of Dolutegravir against HIV-1 in PBMCs (i.e., 0.51 nM), this translates to a cell-based therapeutic index of at least 9,400[1].In Vivo: Following a single intravenous (IV) administration of Dolutegravir, the plasma clearance is low in rats (0.23 mL/min/kg) and monkeys (2.12 mL/min/kg). The half-lives in the rat and monkey are similar, approximately 6 h, and the steady-state volume of distribution (VSS) is low. Following oral administration, Dolutegravir is rapidly absorbed with a high oral bioavailability when administered as a solution to fasted male rats and a single monkey (75.6 and 87.0%, respectively). Dolutegravir exposure (Cmax and AUC) increased with increasing dose following oral administration of a suspension to non-fasted rats up to 250 mg/kg and non-fasted monkeys up to 50 mg/kg, although the increase is less than proportional[2].

Moss L, et al. The comparative disposition and metabolism of dolutegravir, a potent HIV-1 integrase inhibitor, in mice, rats, and monkeys. Xenobiotica. 2015 Jan;45(1):60-70. Kobayashi M, et al. In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother. 2011 Feb;55(2):813-21.