CCT-251236

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

一种有效的口服 Pirin 配体 (Ki=28 nM)，可阻断 HSF1 介导的 HSP72 和 HSP27 诱导。

A potent, orally available Pirin ligand (Ki=28 nM), blocks the HSF1-mediated induction of both HSP72 and HSP27; inhibits the induction of HSP72 at the mRNA level, blocks the induction of HSPA1A gene expression with IC50 of 40 nM, inhibits SK-OV-3 cells proliferation with GI50 of 1.1 nM; displays efficacy in a human ovarian carcinoma xenograft model.

CCT251236 (0-100 nM; 24hours) displays a desired balance of in vitro properties, while maintaining excellent cellular activity with a pIC50=7.73 ± 0.07 (IC50=19 nM) for inhibition of HSF1-mediated HSP72 induction. The free GI50?is 1.1 nM in SK-OV-3 cells that calculated from the free fraction in the cell assay.CCT251236 (0-100 nM; 24 hours) blocks 17-AAG induced he HSF1-mediated heat-shock proteins, HSP72 and HSP27 expression as a concentration manner in SK-OV-3 cells.CCT251236 (0-100 nM; 24 hours), pre-treated with250 nM 17-AAG for 6h, blocks the induction of HSPA1A mRNA by 17-AAG in a dosedependent manner. Western Blot Analysis Cell Line:SK-OV-3 cells Concentration:0 nM; 10 nM; 100 nM Incubation Time:24 hours Result:Inhibited HSP72 and HSP27 expression at the dose of 10 nM.RT-PCRCell Line:SK-OV-3 cells Concentration:0 nM; 10 nM; 100 nM and 1000 nM Incubation Time:24 hours Result:Decreased HSPA1A mRNA level.

CCT251236 (oral adminstation; 5 or 20 mg/kg) in nontumor bearing immunocompetent BALB/c mice exhibits free?Cav0-24h?value of 2.0 nM and 1.2 nM, respectively.CCT251236 (oral adminstation; 20 mg/kg; 33 days)has aclear therapeutic efficacy in mice with a tumor growth inhibition (%TGI) of 70% based on final tumor volumes. After 33 days, the mean tumor weights decreases 64% when compares to control group. In addition, the compound’s basicity and high volume of distribution shows in tumor withtumor concentrations of?CCT251236?as high as 940 nM. Animal Model:Athymic mice with SK-OV-3 cells Dosage:20 mg/kg; 33 days Administration:Oral adminstation Result:Was efficacious in SK-OV-3 cell induced-tumor mice model.

CCT251236

Cytoskeleton/Cell Adhesion Molecules

HSP

HSP

——

——

1693731-40-6

552.631

C32H32N4O5

>98% (HPLC)

DMSO : ≥ 150 mg/mL 271.43 mM

O=C(C1=CC(C=CC(OCCN2CCCC2)=N3)=C3C=C1)NC4=CC(NC(C5=CC(OCCO6)=C6C=C5)=O)=CC=C4C

N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-methylphenyl)-2-(2-(pyrrolidin-1-yl)ethoxy)quinoline-6-carboxamide

(-20℃)

With Ice Pack

≥ 2 years