CDK8/19-IN-1

CDK8/19-IN-1 is a potent, selective and oral bioavailable CDK8/19 dual inhibitor, with IC50s of 0.46 nM, 0.99 nM and 270 nM for CDK8, CDK19 and CDK9, respectively.

Research Areas >> Cancer

CDK8/CycC:0.46 nM (IC50)

CDK19/CycC:0.99 nM (IC50)

CDK9:270 nM (IC50)

CDK8/19-IN-1 (52h) is a potent CDK8/19 dual inhibitor, with IC50s of 0.46 nM, 0.99 nM and 270 nM for CDK8, CDK19 and CDK9, respectively. CDK8/19-IN-1 also weakly inhibits CDK2, with 62% inhibition at 1 μM. CDK8/19-IN-1 (1 μM) shows >50% inhibition against GSK3β, PLK1, ASK1, CK1δ, PKA, ROCK1, PKCθ, CDC7. CDK8/19-IN-1 shows Kds of 25, 46, 81, 86, 97, 160 and >3000 nM for CDK19, CDK8, DYRK1B, HASPIN, YSK4, HIPK1 and EPHA3, respectively. CDK8/19-IN-1 displays potent antitumor activity, with GI50 of 0.43-2.5 nM for colon, multiple myeloma, acute myelogenous leukemia (AML), lung cancer cells[1].

CDK8/19-IN-1 (52h; 1.25 mg/kg twice daily or 2.5 mg/kg once daily, p.o.) significantly suppresses tumor growth in mice bearing RPMI8226 human hematopoietic and lymphoid cells[1].

[1]. Ono K, et al. Design and synthesis of selective CDK8/19 dual inhibitors: Discovery of 4,5-dihydrothieno[3',4':3,4]benzo[1,2-d]isothiazole derivatives. Bioorg Med Chem. 2017 Apr 15;25(8):2336-2350.

Abemaciclib(LY2835219) | Ribociclib (LEE011) | Dinaciclib (SCH727965) | THZ1 2HCl | Roscovitine (CYC202) | THZ531 | RO-3306 | Flavopiridol | NVP 2 | BAY-1143572 Racemate | CYC-065 | AZD5438 | BIO | Kenpaullone | SNS-032 (BMS-387032)