CCT-244747

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

一种新型、强效、高选择性、口服活性、ATP 竞争性 CHK1 抑制剂，生化 IC50 为 8 nM；对 FLT3 的选择性高出 75 倍，对 CHK2 和 CDK1 的选择性高出 1,000 倍以上。

A novel, potent, highly selective, orally active, ATP competitive CHK1 inhibitor with biochemical IC50 of 8 nM; displays 75-fold selectivity against FLT3 and >1,000-fold selectivity against CHK2 and CDK1; inhibits cellular CHK1 activity (IC50=29-170nM), significantly enhances the cytotoxicity of several anticancer drugs and abrogates drug-induced S and G2 arrest in multiple tumor cell lines; enhances antitumor activity of gemcitabine and irinotecan in vivo.

CCT244747 poorly inhibits CHK2 (IC50 >10 μM) and CDK1 (IC50 >10 μM). CCT244747 has potent activities against CHK1, RSK1, RSK2, AMPK, BRSK1, IRAK1,and TrkA, with >80% inhibition. CCT244747 (10 μM) exhibits <25% inhibition of the other ion channels including hNav1.5, hKv4.3/hKChIP2, hCav1.2, hKv1.5, hKCNQ1/hminK, hHCN4. CCT244747 inhibits FLT3 with an IC50 of 600 nM. CCT244747 (0.5 μM) overcomes genotoxic-induced S and G2 cell cycle arrest in human colon cancer cell lines. CCT244747 inhibits cellular CHK1 function with IC50s ranging from 29 nM to 170 nM for cellular G2 checkpoint abrogation (MIA, mitosis induction assay) in HT29, SW620, MiaPaCa-2, and Calu6 cell lines; the GI50s are between 0.33 and 3μM. CCT244747 (0.3 μM) inhibits SN38 and gemcitabine-induced CHK1 activity in HT29 and SW620 colon cancer cell lines and this correlates with abrogation of cell cycle arrest, induction of DNA damage and apoptosis. CCT244747 (0.5-2.0 μM) increases the sensitivity of bladder and head and neck cancer cell lines (T24, RT112 and Cal27) to radiation.

CCT244747 (100 mg/kg po, qd7d) significantly reduces tumor burden in human tumor xenografts. CCT244747 (100-300 mg/kg, po) inhibits gemcitabine-induced pS296 CHK1 for up to 24 h in HT29 colon tumor xenografts. CCT244747 (75 mg/kg, p.o.) in combination with gemcitabine has potent antitumor effects in HT29 colon tumor xenografts and Calu6 human lung cancer xenografts. CCT244747 (150 mg/kg p.o.) also shows antitumor activities with irinotecan in SW620 human colon tumor xenografts. CCT244747 (100 mg/kg, p.o.) exhibits radiosensitization activity in Cal27 xenografts.

CCT 244747 | CCT244747

Angiogenesis

Chk

Chk

Cancer

——

1404095-34-6

408.457

C20H24N8O2

>98% (HPLC)

10 mM in DMSO

N#CC1=NC=C(N=C1O[C@@H](CN(C)C)C)NC2=NC=C(C(OC)=C2)C3=CN(N=C3)C

2-Pyrazinecarbonitrile, 3-[(1R)-2-(dimethylamino)-1-methylethoxy]-5-[[4-methoxy-5-(1-methyl-1H-pyrazol-4-yl)-2-pyridinyl]amino]-

(-20℃)

With Ice Pack

≥ 2 years