CDK9-IN-19

CDK9-IN-19 is a highly potent and selective CDK9 inhibitor with an IC50 value of 2.0 nM. CDK9-IN-19 has excellent cellular antiproliferative activity, moderate pharmacokinetic property and low hERG inhibition. CDK9-IN-19 significantly induces tumour growth inhibition in an MV4-11 xenograft mice model. CDK9-IN-19 can be used for researching acute myeloid leukaemia (AML)[1].

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> CDK

CDK9/cyclinT1:2 nM (IC50)

CDK9-IN-19 (compound 30i) has antiproliferative activity against a panel of human tumor cell lines with IC50 ranks of 0.08~0.64 μM (for example: Hep G2, HCT-116, SW620, A549, MV-4-11, et al.)[1]. CDK9-IN-19 has low hERG inhibitory activity (IC50=10080 nM) and over 5000-fold selectivity for CDK9[1]. CDK9-IN-19 (0.1-0.8 μM; 24 h) reduces the expression levels of Mcl-1 and c-Myc[1]. Western Blot Analysis[1] Cell Line: MV4-11 Concentration: 0.1, 0.2, 0.4 and 0.8 μM Incubation Time: 24 h Result: Clearly reduced the expression levels of Mcl-1 and c-Myc at 0.1 μM, and completely reduced at 0.2-0.8 μM.

CDK9-IN-19 (10, 20 or 40 mg/kg; IV, for 32 days) significantly suppresses the tumour progression in MV4-11 xenograft model[1]. Pharmacokinetic Parameters of CDK9-IN-19 in ICR mice[1]. PO (30 mg/kg) IV (2 mg/kg) T1/2 (h) NR 0.23 Tmax (h) 0.25 - C0 (ng/mL) - 3060 Cmax (ng/mL) 665 - AUC0-t (ng/mL·h) 1200 560 AUC0-∞ (ng/mL·h) NR 561 CL (L/h/kg) - 3.56 VdSS (L/kg) - 0.67 F (%) 14.3 - Animal Model: Female BALB/c nude mice (injected with MV4-11)[1] Dosage: 10, 20 or 40 mg/kg Administration: IV, for 32 days Result: Significantly suppressed the tumour progression and tumour growth inhibition (TGI) values up to 100% from days 14-32 at 40 mg/kg.

[1]. Xu J, et al. Discovery of coumarin derivatives as potent and selective cyclin-dependent kinase 9 (CDK9) inhibitors with high antitumour activity. Eur J Med Chem. 2020 Aug 15;200:112424.