1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECCT-251921Cat. No.: HY-19984CAS No.: 1607837-31-9分式: CHClNO分量: 410.9作靶點(diǎn): CDK作通路: Cell Cycle/DNA Damage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 : 28 mg/mL (68.14 mM)* means soluble, but

2、 saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.4337 mL 12.1684 mL 24.3368 mL5 mM 0.4867 mL 2.4337 mL 4.8674 mL10 mM 0.2434 mL 1.2168 mL 2.4337 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 CCT-251921有效，選擇性，有服活性的CDK8抑制劑；IC50值為2.3 nM。IC50 & Target CDK8

3、CDK192.3 nM (IC50) 2.6 nM (IC50)體外研究CCT-251921 has acceptable aqueous solubility and demonstrates minimal activity when tested in a panel of1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemE55 receptors, ion channels, and enzymes at 1 M and in a panel of 279 kinases; weak inhibition of CYPs isobserve

4、d. CCT-251921 demonstrates potent inhibition of reporter-based readouts measuring basal WNTpathway activity in human cancer cell lines that have constitutively activated WNT pathway signaling:LS174T (-catenin mutant), SW480 and Colo205 (APC mutant) or PA-1 human teratocarcinoma cells thatare WNT lig

5、and dependent 1.體內(nèi)研究 CCT-251921 shows improved oral pharmacokinetics and pharmaceutical properties in order to facilitatefurther evaluation of CDK8/19 pharmacology and progression into preclinical efficacy and safety studies. InAPC-mutant SW620 human colorectal carcinoma xenograft model, CCT-251921

6、treatment reduces micetumor weight (54.2%) at day 15. The inhibition of STAT1SER727 phosphorylation is maintained for morethan 6 h after the last dose 1.PROTOCOLCell Assay 1 7dF3 cells are treated with CCT-251921 ranging in final concentration from 90 M to 0.3 nM. After 2 h offurther incubation, -oe

7、stradiol is added to a final concentration of 10 M. The cells are incubated and then25 L of luciferase reagent is added and mixed. After leaving the plate for 60 min at room temperature,luminescence is read on a plate luminescence reader 1.MCE has not independently confirmed the accuracy of these me

8、thods. They are for reference only.Animal Mice: Animals are dosed orally by gavage every 24 h at 0.1 mL per 10 g body weight. Tumors are measuredAdministration 1 three times weekly by Vernier calipers and body weights recorded. At the end of the study, animals are culledat intervals: 3 control and 3

9、 treated at 1, 2, 6, and 24 h after the final dose. Heparinized blood is collected bycardiac puncture, spun, and plasma snap frozen for analysis of compound exposure. Tumors are excised,weighed and samples snap frozen for compound quantification and PD analyses. The 30 mg/kg q.d.schedule is well tol

10、erated with no significant body weight loss. Tumor growth is significantly inhibited 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Mallinger A, et al. Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19. J Med Chem. 2016 Feb 11;59(3):1078-101.McePdfHeightCaution: Product has not been fully