KPT-6566

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

KPT-6566是一种新型选择性共价pin1抑制剂，KPT-6566对PIN1 PPIase结构域的IC50为640 nM，Ki为625.2 nM，并具有抗癌活性。

KPT-6566 is a novel selective covalent pin1 inhibitor KPT-6566 shows an IC50 of 640?nM and a Ki of 625.2 nM for PIN1 PPIase domainand has anti-cancer activity.

KPT-6566 (1-5 μM; 0-8 d) inhibits WT fibroblasts proliferation.KPT-6566 (0-10 μM; 48 h) inhibits normal breast epithelial cells and cancer cells viability via a PIN1-dependent manner.KPT-6566 (0-10 μM; 48 h) affects hyperphosphorylated pRB level, Cyclin D1 and PIN1 concentration.KPT-6566 (2.5-5 μM; 48 h) inhibits the mut-p53, NOTCH1 and NRF2 pathways.KPT-6566 (0-5 μM; 48 h) induces DNA damage via a PIN1-dependent way. Cell Proliferation AssayCell Line:Immortalized fibroblasts derived from WT and Pin1 KO mouse embryos Concentration:1 and 5 μM Incubation Time:0-8 days Result:Dose-dependently inhibited proliferation of WT fibroblasts, while showed no effect on Pin1 KO fibroblasts.Cell Viability Assay Cell Line:MCF10A, HMEC, HeLa, LNCaP, SKOV-3, PANC-1, PC-3, MDA-MB-468 and MDA-MB-231 cellsConcentration:0-10 μM Incubation Time:48 hoursResult:Inhibited normal breast epithelial cells and cancer cells viability even at a low concentration and increased the concentration of PIN1 in MDA-MB-468, SKOV-3, PC-3, LNCaP and PANC-1.Western Blot Analysis Cell Line:Immortalized fibroblasts derived from WT and Pin1 KO mouse embryos and PIN1 KO MDA-MB-231 cells Concentration:0-10 μM Incubation Time:48 hours Result:Decreased hyperphosphorylated pRB and Cyclin D1 levels, dose- and time-dependently promoted degradation of PIN1 .Western Blot Analysis Cell Line:MDA-MB-231, MCF10A, MDA-MB-468 and MDA-MB-231 cells Concentration:0, 2.5 and 5 μM Incubation Time:48 hours Result:Dose-dependently increased H2AX phosphorylation and caused H2AX phosphorylationin MCF10A, MDA-MB-468 and MDA-MB-231 cell lines. Increased H2AX phosphorylation while other inhibitors such as ATRA, PiB and Juglone disabled to induce H2AX phosphorylation at same concentration. Achieved DNA damage through formation of DNA adducts.RT-PCR Cell Line:MDA-MB-231 cells Concentration:2.5 and 5 μM Incubation Time:48 hours Result:Dose-dependently inhibitd the activation of mut-p53 and NOTCH1 pathways which are controlled by PIN1. Inhibitd the expression of cFOS HO1, NQO1, TXNRD1 and DNAJAB, and induced cellular responses to oxidative stress.

KPT-6566 (5 mg/kg; i.p. once a day for 26 days) shows no toxicity to mice. Animal Model:6-week-old female mice with 1 million of MDA-MB-231Luc6 cells injection Dosage:5 mg/kg Administration:Intraperitoneal injection; 5 mg/kg once a day; for 26 days Result:Exibited no sign of local or systemic and organ toxicity by post mortem morphologic analyses.

——

Others

Other Targets

PIN1 PPIase

——

——

881487-77-0

443.5

C22H21NO5S2??

>98% (HPLC)

DMSO:120 mg/mL?(270.55 mM)

CC(C)(C)c1ccc(cc1)S(=O)(=O)\N=C1/C=C(SCC(O)=O)C(=O)c2ccccc12

——

(-20℃)

With Ice Pack

≥ 2 years