Dolutegravir-sodium-GSK-1349572A-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEDolutegravir sodiumCat. No.: HY-13238ACAS No.: 1051375-19-9Synonyms: GSK-1349572A分式: CHFNNaO分量: 441.36作靶点: HIV Integrase; HIV作通路: Metabolic Enzyme/Protease; Anti-infection储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 month

2、s-20C 1 month溶解性数据体外实验 DMSO : 4.5 mg/mL (10.20 mM)H2O : 0.1 mg/mL (insoluble)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.2657 mL 11.3286 mL 22.6572 mL5 mM 0.4531 mL 2.2657 mL 4.5314 mL10 mM 0.2266 mL 1.1329 mL 2.2657 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注

3、意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Dolutegravir钠盐HIV蛋酶强效抑制剂，IC50值为2.7nM，对Raltegravir耐药突变型HIV毒株Y143R,Q148K, N155H,和G140S/Q148H也有定的抑制作。IC50 & Target IC50: 2.7 nM (HIV-1 integrase) 11/3 Master of Small Molecules 您边的抑制剂师www.MedChemE体外研究 The EC50 of Dolutegravir (S/GSK1349572) against HIV-1 is 0.51 nM in

4、 PBMCs, 0.71 nM in MT-4 cells, and2.2 nM in the PHIV assay, which uses a pseudotyped self-inactivating virus. The 50% cytotoxicconcentrations (CC50) for Dolutegravir in proliferating IM-9, U-937, MT-4, and Molt-4 cells are 4.8, 7.0, 14,and 15 M, respectively. In unstimulated and stimulated PBMCs, th

5、e CC50 are 189 M and 52 M,respectively. Based on the EC50 of Dolutegravir against HIV-1 in PBMCs (i.e., 0.51 nM), this translates to acell-based therapeutic index of at least 9,400 1.体内研究 Following a single intravenous (IV) administration of Dolutegravir, the plasma clearance is low in rats (0.23mL/

6、min/kg) and monkeys (2.12mL/min/kg). The half-lives in the rat and monkey are similar, approximately 6h, and the steady-state volume of distribution (VSS) is low. Following oral administration, Dolutegravir israpidly absorbed with a high oral bioavailability when administered as a solution to fasted

7、 male rats and asingle monkey (75.6 and 87.0%, respectively). Dolutegravir exposure (Cmax and AUC) increased withincreasing dose following oral administration of a suspension to non-fasted rats up to 250mg/kg and non-fasted monkeys up to 50mg/kg, although the increase is less than proportional 2.PRO

8、TOCOLCell Assay 1 In vitro growth inhibition (cytotoxicity) studies are conducted with S/GSK1349572 (0.16, 0.8, 4, and 20 nM) inproliferating human leukemic and lymphomic cell lines (IM-9, U-937, MT-4, and Molt-4) as well as instimulated and unstimulated human PBMCs. ATP levels are quantified by usi

9、ng the CellTiter-Glo luciferasereagent to measure the ability of a compound to inhibit cell growth as an indicator of the compoundspotential for cytotoxicity 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal For rat and monkey PK studies, Doluteg

10、ravir is administered as the free acid or the sodium salt. All doses areAdministration 2 presented in terms of the free acid. Dolutegravir is administered by intravenous (IV) short-term (within 2 min)bolus (1 mg/kg) to three male rats and two male monkeys. For single oral administration, Dolutegravi

11、r as asolution (5 mg/kg) is administered to three fasted male rats and two fasted male monkeys. Dolutegravir isadministered as single oral doses of 5, 50, 100, and 250 mg/kg to non-fasted male rats (n=2/dose level) and3, 10, and 50 mg/kg to non-fasted female monkeys. For intravenous administration,

12、blood samples arecollected from rats (0.2 mL via jugular vein cannula) and monkeys (approximately 0.2 or 0.5 mL viasaphenous vein in a hindlimb) into Na2EDTA-treated syringes at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 h. Fororal administration, samples are collected at 0.25 (rats only), 0.5, 1, 2, 4

13、, 6 rats (solution and suspension)and monkey (solution only), 8, and 24 h. Following collection, the blood is immediately put on wet ice andthen centrifuged within an hour at 1740 g for 10 min at 4C to obtain plasma. All samples are stored atapproximately -20C or colder prior to analysis by using a

14、method based on protein precipitation and LC-MS/MS analysis.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Cell Physiol Biochem. 2016 Jul 21;39(2):639-650.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE J Neuroimmune Pharmacol. 2019 Jul 2

15、3. Toxicol Appl Pharmacol. 2019 Apr 1;368:18-25. Drug Metab Dispos. 2019 May;47(5):535-544. Drug Metab Dispos. 2019 May 8. pii: dmd.118.085993.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Kobayashi M, et al. In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob AgentsChemother. 2011 Feb;55(2):813-21.2. Moss L, et al. The comparative disposition and metabolism of dolutegravir, a potent HIV-1 integrase inhibitor, in mice, rats, andmonkeys