3-Methylthienyl-carbonyl-JNJ-7706621 is a highly potent and selective inhibitor of cyclin-dependent kinase (CDK), showing IC50 values of 6.4 nM for CDK1/cyclin B and 2 nM for CDK2/cyclin A. It also exhibits potent inhibition of GSK-3 (IC50 = 0.041 μM) and moderate inhibition of CDK4, VEGF-R2, and FGF-R2 (IC50 = 0.11 μM, 0.13 μM, and 0.22 μM, respectively), making it significant for cancer research.

CDK4:0.11 μM (IC50), VEGFR2:0.13 μM (IC50), CDK1-CyclinB:6.4 nM (IC50), FGFR2:0.22 μM (IC50), CDK2-CyclinA:2 nM (IC50), GSK-3:41 nM (IC50)

3-Methylthienyl-carbonyl-JNJ-7706621 demonstrates significant inhibitory activity against GSK-3 with an IC50 value of 0.041 μM and displays moderate inhibitory effects on CDK4, VEGF-R2, and FGF-R2 with IC50 values of 0.11 μM, 0.13 μM, and 0.22 μM, respectively[1]. Additionally, this compound effectively hinders the proliferation of various cancer cell lines, including HeLa, HCT-116, A375, SK-OV-3, MDA-MB-231, and PC-3, showcasing IC50 values of 0.28 μM, 0.25 μM, 0.45 μM, 0.75 μM, 0.59 μM, and 0.12 μM, respectively[1].

Administering 3-Methylthienyl-carbonyl-JNJ-7706621 at dosages of 75-125 mg/kg intraperitoneally (i.p.) once daily for 32 days significantly reduced A375 human melanoma tumor growth and increased survival in male athymic nude mice. The compound demonstrated oral bioavailability in nude mice (2%), rats (8%), and dogs (63.3%), with terminal elimination half-lives of 1.70 hours in nude mice, 2.20 hours in rats, and 2.36 hours in dogs. Additionally, after oral administration at doses of 30 mg/kg for mice and rats, and 10 mg/kg for dogs, peak concentration (Cmax) values were observed at 0.21 μM in nude mice, 2.5 μM in rats, and 4.58 μM in dogs. Following intravenous administration at 3 mg/kg for mice and rats, and 1 mg/kg for dogs, the compound showed terminal elimination half-lives of 0.51 hours in nude mice, 0.64 hours in rats, and 3.89 hours in dogs. Cmax values were 6.4 μM in nude mice, 23.2 μM in rats, and 2.19 μM in dogs, while the area under the curve (AUC) was 3.2 μM·h for nude mice, 11.4 μM·h for rats, and 2.45 μM·h for dogs. The result was a notable reduction in tumor growth and an extension of survival by approximately 3 weeks compared to the control group.