R-547

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

一种有效的、选择性的 ATP 竞争性 CDK 抑制剂，对于 CDK1/2/4 的 Ki 值分别为 1/3/1 nM。

A potent, selective and ATP-competitive CDK inhibitor with Ki of 1/3/1 nM for CDK1/2/4, respectively; has no activity against a large panel of serine/threonine and tyrosine kinases; inhibits the growth of various human tumor cell lines (HCT116 cell line IC50=80 nM), blocks G1 and G2 phases, induces apoptosis and reduces phosphorylation of Rb; demonstrates significant in vivo efficacy in the HCT116 human colorectal tumor xenograft model in nude mice.Solid Tumors Phase 1 Discontinued.

Cell Cytotoxicity Assay Cell Line:Human tumor cell lines (MDA-MB-468, MDA-MB-435, MCF-7, HCT116, SW480, RKO, HT-29, HCT15, H460a, C33A, DU145, OSA-CL, LOX, JEKO-1, REC-1)Concentration:MTT assay Incubation Time:5 days Result:Has potent in vitro antiproliferative activity.Cell Cycle Analysis Cell Line:R547, HCT116 Concentration:0.1 μM, 0.2 μM, 0.6 μM Incubation Time:20 hours Result:Decrease in BrdUrd incorporation and in percentage S phase in a dose-dependent, indicative of a cell cycle block in G1-S plus G2-M.Western Blot Analysis Cell Line:HCT116 cells Concentration:0.1 μM, 0.2 μM, 0.6 μM Incubation Time:24 hours, 48 hours, 72 hours Result:Showed a band corresponding to a p48/retinoblastoma fragment that becomes more intense at 48 and 72 hours.

Animal Model:13-14 weeks old female immunodeficient nude mice (23-25 g), with HCT116/H460a/MDA-MB-435/DU145/LOX/A549 cells xenograft Dosage:40 mg/kg Administration:Oral administration; daily; for 3-weeks Result:Showed antitumor activity in all of the models in this study.

R547

Cell Cycle/DNA Damage

CDK

CDK1/CyclinB| CDK2/CyclinE| CDK4/CyclinD1| PKA

Cancer

Solid Tumors

741713-40-6

441.4522

C18H21F2N5O4S

>98% (HPLC)

10 mM in DMSO

O=C(C1=CN=C(NC2CCN(S(=O)(C)=O)CC2)N=C1N)C3=C(OC)C=CC(F)=C3F

Methanone, [4-amino-2-[[1-(methylsulfonyl)-4-piperidinyl]amino]-5-pyrimidinyl](2,3-difluoro-6-methoxyphenyl)-

(-20℃)

With Ice Pack

≥ 2 years