Q203-IAP6-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEQ203Cat. No.: HY-101040CAS No.: 1334719-95-7Synonyms: IAP6; Telacebec分式: CHClFNO分量: 557.01作靶點(diǎn): Bacterial作通路: Anti-infection儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 20 mg/mL (35.91 mM

2、; Need ultrasonic)H2O : 90% (20% SBE-CD in saline)Solubility: 2 mg/mL (3.59 mM); Suspended solution; Need ultrasonic1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 Q203（IAP6）是中氮雜吡啶酰胺化合物。 在培養(yǎng)基中抑制結(jié)核分枝桿菌H37Rv活性的MIC50值為2.7 nM。IC50 & Target MIC50: 2.7 nM (Mycobacterium tuberculosi

3、s H37Rv) 1體外研究 Imidazopyridine amide (IPA) compounds block Mycobacterium tuberculosis growth by targeting therespiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibits the growth of MDR andXDR Mycobacterium tuberculosis clinical isolates in culture broth medium in the low nanomolar

4、 range. Q203is active against the reference strain Mycobacterium tuberculosis H37Rv with MIC50s of 2.7 nM in culturebroth medium and 0.28 nM inside macrophages 1.體內(nèi)研究 Q203 is efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight. Q203displays pharmacokinetic and sa

5、fety profiles compatible with once-daily dosing. Q203 has a bioavailability of90% and a terminal half-life of 23.4 h. The volume of distribution is moderate (5.27 l per kg body weight), andthe systemic clearance is low (4.03 mL/min per kg). After 4 weeks of treatment, reductions of 90%, 99% and99.9%

6、 in M. tuberculosis H37Rv bacterial load is observed in the groups treated with Q203 at 0.4, 2 and 10mg per kg body weight, respectively 1.PROTOCOLAnimal Rats: Sprague Dawley rats are used for pharmacokinetic studies. Compounds (Q203) are given at a dose ofAdministration 1 2 mg per kg body weight in

7、travenously or 10 mg per kg body weight orally. The compounds (Q203) areformulated in 20% TPGS (d- tocopheryl polyethylene glycol 1000 succinate) for repeated-dose studies andin 40% PEG400, pH4 for single-dose studies. Blood samples are taken through the caudal vena cava using1-mL syringes before pe

8、rfusion. Samples are collected from three mice or rats at 0.5, 1, 2, 6, 12, 24 and 48 hpost-dose. Blood samples are centrifuged at 3,200g for 10 min at 4 C. Following centrifugation, plasma iscollected and frozen until further analysis. Compound concentrations are determined by LC-MS 1.Mice: Efficac

9、y of Q203 in a mouse model of established tuberculosis is studied. Bacterial loads areenumerated in the lung of infected mice after 14 d and 28 d of treatment. Q203 is used at 0.4, 2 and 10 mgper kg body weight. Bedaquiline and isoniazid (INH) are used as positive controls at 6.5 and 15 mg per kgbod

10、y weight, respectively. Five mice per group and per time point are used 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Pethe K, et al. Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis. Nat Med. 2013 Sep;19(9):1157-60.McePdfHeightCaution: Product has not been fully val