CDK4/6-IN-14

CDK4/6-IN-14 is a potent and highly selective CDK4 and CDK6 (CDK) inhibitor with IC50s of 10 nM and 16 nM, respectively. CDK4/6-IN-14 exhibits more than 60-fold selectivity over CDKs 1, 2, 7, and 9, and shows high selectivity among other 205 kinases[1].

Research Areas >> Cancer

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

CDK4:10 nM (IC50)

CDK6:16 nM (IC50)

CDK1:>10000 nM (IC50)

CDK2:1045 nM (IC50)

CDK7:2595 nM (IC50)

CDK9:2664 nM (IC50)

CDK4/6-IN-14 (compound 42; 1-6 μM; 5 days) exhibits potent inhibitory activity against the proliferation of breast cancer MCF-7, T47D, and ZR-75-1 cell lines. CDK4/6-IN-14 significantly inhibits growth and clone formation of MCF-7 and T47D cells[1]. CDK4/6-IN-14 (compound 42; 1-6 μM) arrests the cell cycle at the G1 phase of MCF-7 and T47D cells in the dose-dependent manner[1]. CDK4/6-IN-14 (compound 42; 1-6 μM; 24 hours) significantly inhibits the phosphorylation of retinoblastoma (RB), while the expression of RB protein was almost unchanged. In addition, CDK4/6-IN-14 exhibits a concentration-dependent effect to decrease the level of c-MYC and cyclin D1[1]. Cell Cytotoxicity Assay[1] Cell Line: MCF-7 and T47D cells Concentration: 1 μM, 2 μM, 4 μM (T47D cells); 1.5 μM, 3 μM, 6 μM (MCF-7 cells) Incubation Time: 5 days Result: Significantly inhibited growth and clone formation of MCF-7 and T47D cells. Western Blot Analysis[1] Cell Line: MCF-7 and T47D cells Concentration: 1 μM, 2 μM, 4 μM (T47D cells); 1.5 μM, 3 μM, 6 μM (MCF-7 cells) Incubation Time: 24 hours Result: Significantly inhibited the phosphorylation of RB.

CDK4/6-IN-14 (compound 42; 100-150 mg/kg; p.o; once a day; for 23 days) significantly inhibits tumor growth of the MCF-7 xenograft model[1]. CDK4/6-IN-14 (compound 42) exhibits a suitable t1/2 of intravenous and oral administration (2.62 and 3.59 h, respectively). Moreover, the oral bioavailability of CDK4/6-IN-14 is 43%[1]. Pharmacokinetic Parameters of CDK4/6-IN-14 (Compound 42) in Sprague–Dawley Rats[1]. admin. Cmax (ng/mL) AUC0-∞ (h × ng/mL) MRT0-∞ (h) Tmax (h) t1/2 (h) F (%) IV 290.52 372.56 3.50 0.033 2.62 PO 144.11 1612.18 9.11 6 3.59 43Dose: i.v. at 1 mg/kg; p.o. at 10 mg/kg[1] Animal Model: BALB/c nude mice bearing MCF-7 cells[1] Dosage: 100 mg/kg, 150 mg/kg Administration: Orally administertion; once a day; for 23 days Result: Significantly inhibited tumor growth of the MCF-7 xenograft model.

[1]. Weijiao Chen, et al. Discovery, Optimization, and Evaluation of Selective CDK4/6 Inhibitors for the Treatment of Breast Cancer. J Med Chem. 2022 Nov 24;65(22):15102-15122.