BS-194

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

BS-194 是一种有效的、选择性的、口服生物活性 CDK2 抑制剂，IC50 为 2.4 nM，选择性是 CDK7 的 140 倍（IC50=378 nM）；弱抑制 CDK1、CDK5、CDK7 和 CDK9，IC50 分别为 30、30、250 和 90 nM。

BS-194 is a potent, selective, orally bioactive CDK2 inhibitor with IC50 of 2.4 nM, displays 140-fold selectivity over CDK7 (IC50=378 nM); weakly inhibits CDK1, CDK5, CDK7, and CDK9 with IC50 of 30, 30, 250, and 90 nM; shows inhibition of the phosphorylation of CDK substrates, Rb and the RNA polymerase II C-terminal domain, down-regulation of cyclins A, E, and D1, and cell cycle block in the S and G2/M phases; inhibits human tumor xenografts and suppresses CDK substrate phosphorylation.

BS-194 (compound 4k, 72 h) inhibits various cancer cells (MCF-7, MDA-MB-231, MCF-10A, CPLO-205, HCT-116, A549, SaOS2, PC3 ,HepG2, SK-Ov-3) growth, with IC50 values ranging from 100 nM to 1 μM.BS-194 (10 μM, 24 h) promotes cell cycle arrest in in S and G2/M phases in HCT116 cells.BS-194 (10 μM, 24 h) inhibits phosphorylation of CDK substrates, and promotes cyclin loss in HCT116 cells.Cell Cycle Analysis Cell Line:HCT116 Concentration:0, 0.01, 0.1, 1, 10 μMIncubation Time:24 h Result:Showed a significant reduction in G1, and increased in S and G2/M phases.Western Blot Analysis 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.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.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.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. Animal Model:Nude mice bearing MCF-7 cell 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 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)Dosage:10 mg/kg Administration:Intraperitoneal injection, intravenous injection, oral administration Result:Pharmacokinetic profile of BS-194 (compound 4k).

BS 194 | BS194

Angiogenesis

CDK

CDK

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1092443-55-4

385.468

C20H27N5O3

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (259.43 mM)

OC[C@@H](O)[C@@H](NC1=NC2=C(C(C)C)C=NN2C(NCC3=CC=CC=C3)=C1)CO

(2S,3S)-3-[[7-(benzylamino)-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]butane-1,2,4-triol

(-20℃)

With Ice Pack

≥ 2 years