BS194

BS-194 is an orally active, selective and potent CDK inhibitor. BS-194 inhibits CDK2, CDK1, CDK5, CDK7, and CDK9 (IC50s: 3, 30, 30, 250, and 90 nM respectively). BS-194 potently inhibits cancer cells proliferation. BS-194 can be used in the research of cancers like breast cancer, colon cancer[1].

Research Areas >> Cancer

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

CDK2:3 nM (IC50)

CDK1:30 nM (IC50)

CDK5:30 nM (IC50)

CDK7:250 nM (IC50)

CDK9:90 nM (IC50)

BS-194 (compound 4k, 72 h) inhibits various cancer cell growth, with IC50 values ranging from 100 nM to 1 μM[1]. BS-194 (10 μM, 24 h) promotes cell cycle arrest in in S and G2/M phases in HCT116 cells[1]. BS-194 (10 μM, 24 h) inhibits phosphorylation of CDK substrates, and promotes cyclin loss in HCT116 cells[1]. Cell Cycle Analysis[1] Cell Line: HCT116 Concentration: 0, 0.01, 0.1, 1, 10 μM Incubation Time: 24 h Result: Showed a significant reduction in G1, and increased in S and G2/M phases. Western Blot Analysis[1] Cell Line: HCT116 Concentration: 0, 0.1, 10, 20 μM Incubation Time: 0, 0.1, 10, 20 μM Result: Inhibited the phosphorylation of the CDK2 substrate RB (retinoblastoma) at Ser-780, Ser-795, Ser-801, Ser-807/Ser-811, and Thr-821. Inhibited levels of cyclin A, cyclin B, and cyclin D1. Inhibited phosphorylation of Thr-170 of CDK2.

BS-194 (compound 4K, intraperitoneal injection, 5 or 10 mg/kg, twice daily for 14 days) inhibits tumor growth with no apparent toxicity in MCF-7 tumor xenografts[1]. BS-194 (i.p., i.v., p.o., 10 mg/kg) is orally bioavailable, with elimination half-lives of 147 min (i.p.), 210 min (i.v.), and 178 min (p.o.) respectively[1]. BS-194 (oral gavage, 25 mg/mL) reduces rapid RB and PolII (RNA polymerase II) phosphorylation, but recovery within 24 h in nu/nu-BALB/c athymic nude mice[1]. BS-194 (oral gavage, 25 mg/kg, daily for 14 days) inhibits tumor growth in HCT116 tumor xenografts, with no significant loss in animal weights[1]. Animal Model: Nude mice bearing MCF-7 cell[1] Dosage: 5 or 10 mg/kg, twice daily for 14 days. Administration: Intraperitoneal injection Result: Inhibited tumor growth in a dose-dependent manner (30% and 40% reduction at 5 and 10 mg/kg dose, respectively). Animal Model: HCT116 tumor xenografts[1] Dosage: 25 mg/kg, daily for 14 days. Administration: Oral gavage Result: Inhibited tumor growth by 50% reduction at 25 mg/kg. Decreased levels of Rb phosphorylation at Ser807/811 and Thr821 (in resected tumors). Animal Model: Mice (pharmacokinetic assay)[1] Dosage: 10 mg/kg Administration: Intraperitoneal injection, intravenous injection, oral administration Result: Pharmacokinetic profile of BS-194 (compound 4k). administration route dose (mg/kg) bioavail-ability (%) Cmax (min) T1/2 (min) i.p. 10 73 30 147 p.o. 10 88 15 178 administration route dose (mg/kg) T1/2 (min) Cl (mL/min/kg) Vz i.v. 10 210 5 1391

[1]. Dean A Heathcote, et al. A novel pyrazolo[1,5-a]pyrimidine is a potent inhibitor of cyclin-dependent protein kinases 1, 2, and 9, which demonstrates antitumor effects in human tumor xenografts following oral administration. J Med Chem. 2010 Dec 23;53(24):8508-22.