依法韦仑作用机制 - Medchemexpress - MCE中国

1、Product Data SheetEfavirenzCat. No.: HY-10572CAS No.: 154598-52-4分式: CHClFNO分量: 315.68作靶点: Reverse Transcriptase; HIV; Autophagy作通路: Anti-infection; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 38 mg/mL (120.38 mM)* means soluble, but saturation unk

2、nown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 3.1678 mL 15.8388 mL 31.6776 mL5 mM 0.6336 mL 3.1678 mL 6.3355 mL10 mM 0.3168 mL 1.5839 mL 3.1678 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；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验 请根据您的实验动物和

3、给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天 使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可 以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (7.92 mM); Clear solution此案可获得 2.5 mg/mL (7.92 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的

4、实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITYPage 1 of 2 www.MedChemE物活性 Efavirenz种有效的野型 HIV-1 RT 抑制剂，Ki 为 2.93 nM，抑制 HIV-1 复制，IC95 为 1.5 nM。IC & Target Ki: 2.93 nM (HIV-1 RT)1体外研究 Efavirenz (L-743726) is found to be capable of inhibiting, with 95% inhibitory conc

5、entrations of 1.5M, a panel ofnonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs)-resistant mutant viruses, each of which expresses asingle RT amino acid substitution. Efavirenz is also tested for its activity against a variety of polymerase enzymesand is found to be inactive (IC50300M). Ef

6、avirenz effectively inhibits several wild-type T-lymphoid cell line-adapted variants. Identical activity (IC95, 1.5 to 3.0 nM) is seen with wild-type primary isolates of the virus in bothprimary lymphoid and monocytoid cell cultures. Efavirenz also effectively inhibits HIV-1 variants that expressed

7、RTamino acid substitutions which confer the loss of susceptibility to other NNRTIs. For purposes of comparison1.Efavirenz is a non-nucleoside analog reverse transcriptase inhibitor (NNRTI) with IC50 of 60 nM2. Efavirenz inhibitssynthesis using an RNA PPT-primed substrate with an IC50 of 17 nM3.体内研究

8、After i.v. administration, Efavirenz (L-743726) is cleared rapidly from rats, but it is cleared considerably more slowlyfrom monkeys. The large volume of distribution (two to four times the amount of body water) in both species indicates extensive tissue binding. The oral bioavailability in rats is

9、16%. In monkeys, the half-life of Efavirenz afteradministration of a 1 mg/kg i.v. dose exceeded 2.5 h. Efavirenz is well absorbed orally. Administration to monkeysof oral doses as fine suspensions in 0.5% aqueous methylcellulose yields consistently high levels in plasma. A 2.0mg/kg dose produces pea

10、k levels of 0.5M at approximately 3.0 h. The absolute bioavailability is estimated to be42%. A 10 mg/kg dose yields a peak level in plasma of 3.22 M. A 10 mg/kg oral dose given to a single chimpanzeegave concentrations in plasma of 4.12, 2.95, and 2.69 M at 2, 8, and 24 h after dosing, respectively1

11、.PROTOCOLKinase Assay 1 Recombinant RT enzymes are expressed, purified, and assessed for inhibition by Efavirenz (L-743726). Ki and Kiivalues are determined for each enzyme tested. The wild-type RT exhibited exclusively noncompetitive inhibitionkinetics (data not shown), and, therefore, the Ki and K

12、ii values are identical. Pure noncompetitive inhibition is notassumed for the mutant enzymes, and, hence, the values of both Ki and Kii are obtained from the linear mixed-typeinhibition equation. The two- to threefold differences between the Ki and Kii values probably reflect a smallcontribution of

13、competitive inhibition with the mutant RTs1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice1Administration 1 Studies are performed in rats, rhesus monkeys, and a single chimpanzee. For analyses of the drug given to ratsintravenously (i.v.),

14、a group (n=4 or 5) of fasted male Sprague-Dawley rats (weight, 250 to 450 g) receive a bolus (at avolume of 1mL/kg of body weight) of Efavirenz in DMSO via a cannula implanted in the right jugular vein. For oralstudies, rats are dosed by gavage by using a suspension of Efavirenz prepared in 0.5% aqu

15、eous methylcellulose.Similarly, four monkeys receive either an i.v. bolus of the compound in DMSO via the saphenous vein at a volume of0.1 mL/kg or are administered the compound orally in suspension by using a nasogastric tube. Monkeys are fastedfor 18 h prior to dosing. One nonanesthetized, nonfast

16、ed male chimpanzee (weight, approximately 60 kg) is dosedorally by voluntary ingestion by using an aqueous suspension of the compound. In all studies, heparinized blood isobtained at appropriate times. Plasma is separated immediately by centrifugation and is stored at -20C untilanalysis. Plasma samp

17、les are extracted with methylene chloride; this is followed by analysis by high-performanceliquid chromatography.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Page 2 of 3 www.MedChemE Cell Physiol Biochem. 2015;37(6):2496-507. Int J Antimic

18、rob Agents. 2019 Dec;54(6):814-819. Faculty of Pharmacy in Hradec Krlov Department of Pharmacological and Toxicology. University of Oxford. 2019 Jul.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Young SD, et al. L-743, 726 (DMP-266): a novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase.Antimicrob Agents Chemother. 1995 Dec;39(12):2602-5.2. Held DM, et al. Differential susceptibility