CHIR-124

CHIR-124 is a quinolone-based small molecule Chk1 inhibitor, that is structurally unrelated to other known inhibitors of Chk1. It potently and selectively inhibits Chk1 in vitro (IC(50) = 0.0003 micromol/L). CHIR-124 interacts synergistically with topoisomerase poisons (e.g., camptothecin or SN-38) in causing growth inhibition in several p53-mutant solid tumor cell lines as determined by isobologram or response surface analysis. CHIR-124 is a novel and potent Chk1 inhibitor with promising antitumor activities when used in combination with topoisomerase I poisons.

Product information

CAS Number: 405168-58-3

Molecular Weight: 419.91

Formula: C23H22ClN5O

Synonym:

CHIR124

CHIR 124

Chemical Name: 3-(1H-benzo[d]imidazol-2-yl)-6-chloro-4-((1R, 3S, 4R)-quinuclidin-3-ylamino)quinolin-2(1H)-one.

Smiles: O=C1NC2=CC=C(Cl)C=C2C(N[C@@H]2C[N@]3CC[C@@H]2CC3)=C1C1NC2=CC=CC=C2N=1

InChiKey: MOVBBVMDHIRCTG-LJQANCHMSA-N

InChi: InChI=1S/C23H22ClN5O/c24-14-5-6-16-15(11-14)21(25-19-12-29-9-7-13(19)8-10-29)20(23(30)28-16)22-26-17-3-1-2-4-18(17)27-22/h1-6,11,13,19H,7-10,12H2,(H,26,27)(H2,25,28,30)/t19-/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 7 mg/mL(16.67 mM). Water: Insoluble.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

CHIR-124 is a quinolone-based small molecule that is structurally unrelated to other known inhibitors of Chk1. CHIR-124 interacts synergistically with topoisomerase poisons (e.g., Camptothecin or SN-38) in causing growth inhibition in a variety of cancer cell lines, including breast carcinoma (MDA-MB-231 and MDA-MB-435) and colon carcinoma (SW-620 and Colo205), all of which contains the mutant p53 gene. CHIR-124 abrogates the SN-38-induced S and G2-M checkpoints and potentiates apoptosis in MDA-MD-435 breast cancer cells. The abrogation of the G2-Mcheckpoint and induction of apoptosis by CHIR-124 are enhanced by the loss of p53. CHIR-124 also potently targets other kinases such as PDGFR and Flt3 with IC50 of 6.6 nM and 5.8 nM, respectively.

In Vivo:

CHIR-124 potentiates the growth inhibitory effects of Irinotecan by abrogating the G2-M checkpoint and increasing tumor apoptosis in an orthotopic breast cancer xenograft model.

References:

1. Dai Y, et al, Clin Cancer Res, 2010, 16(2), 376-383
2. Tse AN, et al, Clin Cancer Res, 2007, 13(2 Pt 1), 591-602.

Products are for research use only. Not for human use.