图片.png For research use only

Product Infomation
Product NameCHIR-124
CAS No.

405168-58-3

Molecular Weight

419.91

Formula

C₂₃H₂₂ClN₅O

SMILES

ClC1=CC2=C(NC(C(C3=NC4=C(C=CC=C4)N3)=C2N[C@@H]5CN6CCC5CC6)=O)C=C1

Stock statusGet quote



Online consultation: s_qq.png  s_email.png



Product description

Description

CHIR-124 is a potent and selective Chk1 inhibitor with IC50 of 0.3 nM, and also potently targets PDGFR and FLT3 with IC50s of 6.6 nM and 5.8 nM.


IC50 & Target

________________________________________________________________________________________

Chk1

0.3 nM (IC50)


In Vitro

_________________________________________________________________________________________

CHIR-124 is 500- to 5,000-fold less active against other cell cycle kinases, such as cyclin-dependent kinase 2/cyclin A (0.19 μM), cdc2/cyclin B (0.51 μM), and cyclin-dependent kinase 4/cyclin D (2.1 μM). CHIR-124 (≥0.9 nM) in combination with SN-38 (≥0.42 nM) causes significant synergy or >10% deviation from additivity in human cancer cell lines expressing mutant p53, and these values overlap and fall below the IC50s for SN-38 (1.2×10-7 M) and CHIR-124 (2.2×10-7 M), respectively. Moreover, CHIR-124 (100 nM) abrogates the SN-38-induced S and G2-M phase cell cycle checkpoints. CHIR-124 (200 nM) leads to a 2.5-fold elevated level of cdc25A above that of the untreated HCT116 p53−/− cells. The down-regulation of cdc25A induced by SN-38 is completely restored by concurrent or sequential treatment with CHIR-124, proving that CHIR-124 inhibits the Chk1-mediated destruction of cdc25A in whole cells[1]. CHIR-124 occupies the ATP-binding site, inhibits Chk1 (IC50, 0.3 nM) 2,000-fold more potently than Chk2 (IC50, 0.7 μM)[2].

CHIR-124 (10 or 20 mg/kg, p.o.) does not have a significant effect on tumor growth when compared with the vehicle-treated group, but it potentiates the growth inhibitory effect of CPT-11 in a human breast carcinoma xenograft model. The potentiation of the tumor growth inhibitory effect of CPT-11 by CHIR-124 is associated with an increase in apoptosis induction in the tumors. CHIR-124 reverses the suppression of phospho-H3 staining induced by CPT-11, indicating abrogation of the G2-M checkpoint by CHIR-124[1].




Powder-20°C3 years

4°C2 years
In solvent-80°C6 months

-20°C1 month







Peferences:

[1]. Tse AN, et al. CHIR-124, a novel potent inhibitor of Chk1, potentiates the cytotoxicity of topoisomerase I poisons in vitro and in vivo. Clin Cancer Res, 2007, 13(2 Pt 1), 591-602.

[2]. Dai Y, et al. New insights into checkpoint kinase 1 in the DNA damage response signaling network. Clin Cancer Res, 2010, 16(2), 376-383.