Tipranavir-PNU-140690-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETipranavirCat. No.: HY-15148CAS No.: 174484-41-4Synonyms: PNU-140690分式: CHFNOS分量: 602.66作靶点: HIV Protease; HIV作通路: Metabolic Enzyme/Protease; Anti-infection储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解

2、性数据体外实验 Ethanol : 50 mg/mL (82.97 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.6593 mL 8.2966 mL 16.5931 mL5 mM 0.3319 mL 1.6593 mL 3.3186 mL10 mM 0.1659 mL 0.8297 mL 1.6593 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，并请注意储备液的保存式和期限。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

3、请先配制澄的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄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% EtOH 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.15 mM); Suspended solution; Need ultrasonic2. 请依序添加每种溶剂： 10% EtOH 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.15 mM);

4、 Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% EtOH 90% corn oilSolubility: 2.5 mg/mL (4.15 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Tipranavir (PNU-140690) 有效抑制 HIV-1 蛋酶 酶活性和聚化，对抗多种蛋酶抑制剂(PI)的HIV-1分离株具有有效的活性，IC50 为 66-410 nM。IC50 & Target IC50

5、: 66-410 nM (HIV-1 isolates) 1体外研究 Tipranavir (PNU-140690) inhibits the enzymatic activity of HIV-1 protease, blocks the dimerization ofprotease subunits, and exerts potent activity against a wide spectrum of wild-type and multi-PI-resistant HIV-1 variants. When a mixture of 11 multi-PI-resistant (b

6、ut TPV-sensitive) clinical isolates (HIV11MIX), whichinclude HIVB and HIVC, is selected against Tipranavir, HIV11MIX rapidly (by 10 passages HIV11MIXP10)acquires high-level Tipranavir (PNU-140690) resistance and replicates at high concentrations of Tipranavir(PNU-140690). cHIVBI54V and cHIVBI54V/V82

7、T are significantly resistant to Tipranavir (PNU-140690), withIC50s of 2.9 and 3.2 M, respectively, which are 11- and 12-fold increases in comparison to the IC50 againstcHIVB, respectively 1.体内研究 Tipranavir (PNU-140690) is administered orally twice daily and must be given in combination with low-dos

8、eritonavir (RTV) to boost Tipranavir bioavailability. In Tipranavir/r-cotreated mice, the Tipranavir (PNU-140690)abundance in the liver, spleen, and eyes is significantly higher than that in mice treated with Tipranavir alone.Tipranavir (PNU-140690) metabolites accounts for 31 and 38% in the serum a

9、nd liver in the Tipranavir-alonegroup. In Tipranavir (PNU-140690) and Tipranavir (TPV/r)-cotreated mice, only 1 and 2% of metabolites aredetected in the serum and liver. Sprague-Dawley rats are administered a single dose of 14CTipranavir(PNU-140690) with coadministration of RTV. The most abundant me

10、tabolite in feces is an oxidationmetabolite. In urine, no single metabolite is found to be significantly present 2.PROTOCOLAnimal Mice 2Administration 2 All mice (2-4 months old) are maintained under a standard 12-h dark and 12-h light cycle with water andchow provided ad libitum. For metabolomic an

11、alysis, Tipranavir (PNU-140690) (40 mg/kg) is administered viaball-tipped gavage needles, and the mice are housed in separate metabolic cages for 18 h. Urine and fecessamples are collected and stored at 20C for further analysis. For tissue distribution and inhibition studies,three groups of mice are

12、 used and are orally treated with Tipranavir (100 mg/kg), RTV (40 mg/kg), andTipranavir (PNU-140690) (100 mg/kg Tipranavir and 40 mg/kg RTV), respectively. Tissues including the liver,brain, lung, kidney, spleen, and eyes are collected 30 min after treatment and stored at 20C for furtheranalysis.MCE

13、 has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE Talanta. 2018 May 1;181:182-189. Int J Antimicrob Agents. 2019 Aug 31. pii: S0924-8579(19)30241-9. ACS Chem Biol. 2014 Jul 18;9(7):1622-31. Faculty of Pharmac

14、y in Hradec Krlov Department of Pharmacological and Toxicology. University of Oxford. 2019 Jul.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Aoki M, et al. Loss of the protease dimerization inhibition activity of tipranavir (TPV) and its association with the acquisition of resistanceto TPV by HIV-1. J Virol. 2012 Dec;86(24):13384-96.2. Li F, et al. Metabolism-mediated drug interactions associated with ritonavir-boosted tipranavir in mice. Drug Metab Dispos. 20