1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAzaindole 1Cat. No.: HY-10319CAS No.: 867017-68-3Synonyms: TC-S 7001分式: CHClFNO分量: 402.79作靶點(diǎn): ROCK作通路: Cell Cycle/DNA Damage; Stem Cell/Wnt; TGF-beta/Smad儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)

2、據(jù)體外實(shí)驗(yàn) DMSO : 33.33 mg/mL (82.75 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.21 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.21 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 Azaindol

3、e 1有服活性，ATP-競爭型的 ROCK 抑制劑，對(duì)ROCK-1 和 ROCK-2 的 IC50 值分別為0.6 和 1.1nM。IC50 & Target ROCK-1 ROCK-2 TRK FLT30.6 nM (IC50) 1.1 nM (IC50) 252 nM (IC50) 303 nM (IC50)體外研究 Azaindole 1 is a highly potent inhibitor of human ROCK-1 and ROCK-2, with IC50s of 0.6 and 1.1nM,respectively, and also inhibits murine RO

4、CK-2 or rat ROCK-2 with IC50s of 2.4 and 0.8nM, respectively.Azaindole 1 also inhibits receptor tyrosine kinases TRK and FLT3, with IC50s of 252 and 303nM,respectively, but shows slight inhibition of MLCK and ZIP-kinase with IC50s of 7.4M and 4.1M,respectively. Azaindole 1 induces vasorelaxation in

5、vitro, and suppresses the phenylephrine-inducedcontraction of rabbit saphenous artery in a concentration dependent manner with an IC50 value of 65nM 1.體內(nèi)研究 Azaindole 1 (0.03, 0.1, 0.3mg/kg, i.v.) results in a dose-dependent and long-lasting decrease in bloodpressure in anaesthetized normotensive rat

6、s. Azaindole 1 (3 and 10mg/kg, p.o.) decreases blood pressuredose-dependently and persistently both in normotensive and hypertensive rats, and shows such effects evenat 1mg/kg in hypertensive rats. Azaindole 1 (0.1 and 0.3mg/kg, i.v. bolus injections) causes decreased meanarterial blood pressure in

7、a dose-related manner and only leads to a moderate and dose-independentincrease in heart rate of anaesthetized dogs 1.PROTOCOLKinase Assay 1 Human ROCK-1 and ROCK-2, murine ROCK-2, human ZIP-kinase and human MLC kinase (MLCK)(aa1425-1771) are preincubated for 10min with test compounds in 0.05mL of 5

8、0mM Tris/HCl, pH 7.5, 1mMEDTA, 5mM MgCl2 and 0.06% CHAPS or 50mM HEPES, pH 7.4, 10mM Mg acetate, 1mM dithiothreitol,0.3mM CaCl2, 1M calmodulin (MLCK). As substrate following peptides are used: RRLSSLRA (ROCK; S6peptide), KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK (ZIP-kinase; long S6 peptide) andKKRAARATSNVFA

9、 (MLCK; MLC peptide). After 10min preincubation with dimethyl sulphoxide (DMSO)(0.1% final concentration) or with increasing amounts of Azaindole 1 (final concentration 0.1nM-3M), theassays are initiated with 33PATP (3000mCi/mmol) (10M). After 20min incubation, the reaction isterminated by incubatio

10、n at 95C for 10min. After centrifugation at 10000g for 1min, an aliquot of eachincubation is spotted on paper matts. The papers are dried and subsequently washed twice in distilled water.After being dried, the papers are coated with scintillator and counted for radioactivity. Inhibition curves arean

11、alysed by nonlinear regression using GraphPad Prism 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Male Wistar rats weighing 300-350g are anaesthetized with thiopental 100mg/kg intraperitoneally (i.p.). AAdministration 1 tracheotomy is perform

12、ed and catheters are inserted into the femoral artery for blood pressure and heart ratemeasurements and into the femoral vein for test drug administration. The animals are ventilated with room airand their body temperature is controlled. Azaindole 1 is administered intravenously (i.v.) in doses of 0

13、.03-0.12/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEmg/kg in a solution of Transcutol/Cremophor EL/physiological saline (19/10/80 = v/v/v). The vehicleTranscutol/Cremophor EL/physiological saline (19/10/80 = v/v/v) without test drug is used as control. Thevolume administered is 1mL/kg. Six anima

14、ls are treated per group 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) JCI Insight. 2018 Jun 7;3(11). pii: 98921.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Kast R, et al. Cardiovascular effects of a novel potent and highly selective azaindole-based inhibitor of Rho-kinase. Br J Pharmacol.2007 Dec;152(7):1070-80. Epu