CCT-251921是有效，选择性，有口服活性的CDK8抑制剂；IC₅₀值为2.3 nM。

CCT-251921 is a potent, selective, and orally bioavailable CDK8 inhibitor with an IC 50 of 2.3 nM.

Solid

CDK8 2.3 nM (IC50) CDK19 2.6 nM (IC50

CCT-251921 has acceptable aqueous solubility and demonstrates minimal activity when tested in a panel of 55 receptors, ion channels, and enzymes at 1 μM and in a panel of 279 kinases; weak inhibition of CYPs is observed. CCT-251921 demonstrates potent inhibition of reporter-based readouts measuring basal WNT pathway activity in human cancer cell lines that have constitutively activated WNT pathway signaling: LS174T (β-catenin mutant), SW480 and Colo205 (APC mutant) or PA-1 human teratocarcinoma cells that are WNT ligand dependent. has not independently confirmed the accuracy of these methods. They are for reference only.

CCT-251921 shows improved oral pharmacokinetics and pharmaceutical properties in order to facilitate further evaluation of CDK8/19 pharmacology and progression into preclinical efficacy and safety studies. In APC-mutant SW620 human colorectal carcinoma xenograft model, CCT-251921 treatment reduces mice tumor weight (54.2%) at day 15. The inhibition of STAT1 phosphorylation is maintained for more than 6 h after the last dose. has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. 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.

In Vitro: DMSO : 25 mg/mL (60.84 mM; ultrasonic and warming and heat to 60°C)配制储备液