CDK8/19-IN-1

• CAT Number: I020047
• CAS Number: 1818427-07-4
• Molecular Formula: C19H18N4O4S2
• Molecular Weight: 430.50
• Purity: ≥95%
• Synonyms: 8-[6-(2-methoxyethylcarbamoyl)pyridin-3-yl]oxy-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide
• InChI: InChI=1S/C19H18N4O4S2/c1-26-7-6-21-18(25)13-5-3-11(9-22-13)27-19-14-12(16(28-19)17(20)24)4-2-10-8-23-29-15(10)14/h3,5,8-9H,2,4,6-7H2,1H3,(H2,20,24)(H,21,25)
• InChIKey: NENJFZKQHYXRDQ-UHFFFAOYSA-N
• SMILES: COCCNC(=O)C1=NC=C(C=C1)OC2=C3C(=C(S2)C(=O)N)CCC4=C3SN=C4

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.
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].

Reference

[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.
 [Content Brief]