BI-224436 _HIV 抑制剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBI 224436Cat. No.: HY-18595CAS No.: 1155419-89-8分式: CHNO分量: 442.51作靶点: HIV; HIV Integrase作通路: Anti-infection; Metabolic Enzyme/Protease储存式: Powder -20C 3 years4C 2 years* 该产品在溶液状态不稳定，建议您现现配，即刻使。溶解性数据体外实验 DMSO : 50 mg/mL (112.99

2、mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.2598 mL 11.2992 mL 22.5984 mL5 mM 0.4520 mL 2.2598 mL 4.5197 mL10 mM 0.2260 mL 1.1299 mL 2.2598 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；该产品在溶液状态不稳定，建议您现现配，即刻使。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验

3、结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.65 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.65 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% c

4、orn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (5.65 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 BI 224436种新型的HIV-1催化性位点整合酶抑制剂，对HIV-1实验室 株的EC50值于15 nM。IC50 & Target EC50: 15 nM (HIV-1) 1体外研究 BI 224436 has cellular cytotoxicity of more than 90 M. BI 224436 has a low, 2.1-

5、fold decrease in antiviralpotency in the presence of 50% human serum. BI 224436 retains full antiviral activity against recombinantviruses encoding INSTI resistance substitutions N155S, Q148H, and E92Q. BI 224436 displays an additiveeffect in combination with most approved antiretrovirals, including

6、 INSTIs. BI 224436 has drug-like in vitroabsorption, distribution, metabolism, and excretion (ADME) properties, including Caco-2 cell permeability,solubility, and low cytochrome P450 inhibition 1.体内研究 BI 224436 exhibits excellent pharmacokinetic profiles in rat (clearance as a percentage of hepatic

7、flow CL,0.7%; bioavailability F, 54%), monkey (CL, 23%; F, 82%), and dog (CL, 8%; F, 81%) 1.PROTOCOLKinase Assay 1 BI 224436 is dissolved in acetonitrile-methanol (50:50, vol/vol) to achieve a concentration of 1.5 mM.Phosphate buffer (pH 7.4), cofactor, and test substance or isoform-selective inhibi

8、tors are added to 96-wellplates and are prewarmed to 37C for 10 min. Cofactor concentrations are 1.3 mM NADP, 3.3 mM glucose-6-phosphate, and 0.4 U/mL glucose-6-phosphate dehydrogenase. Reactions are initiated by the addition ofprewarmed (37C) enzyme and substrate. Reaction mixtures are incubated at

9、 37C and terminated by theaddition of 0.038 ml of 40:40:20 (vol/vol) methanolacetonitrile0.5 M Tris buffer. Formation of thefluorescent metabolites is measured using a microplate spectrofluorometer at specific excitation andemission wavelengths. The IC50 is determined using the 96-well 32 procedure

10、supplied with the SASsoftware 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats: For oral PK studies, BI 224436 is administered in a suspension of 0.5% (wt/vol) methyl cellulose (MC),Administration 1 0.3% (vol/vol) Tween 80, and 1% (vol/vol)

11、 N-methyl-2-pyrrolidine (MP) in water. For i.v. dosing, BI 224436 isdissolved in 70% PEG 40030% water (vol/vol). The appropriate amount of BI 224436 is dissolved in PEG400 with sonication. The rats receive a single i.v. dose of 0.2 mg/kg of body weight (1 mL/kg) via the jugularvein as a bolus or rec

12、eived a single oral dose of 0.4 mg/kg (10 mL/kg) administered by gavage. Bloodsamples are obtained at 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 32 h after dosing for analysis 1.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 Elife. 20

13、19 May 23;8. pii: e46344.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE J Biol Chem. 2017 Dec 1;292(48):19814-19825.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Fenwick C, et al. Preclinical profile of BI 224436, a novel HIV-1 non-catalytic-site integrase inhibitor. Antimicrob Agents Chemother.2014 Jun;58(6):3233-44.McePd