CHIR-124

Chk1 inhibitor,novel and potent CAS# 405168-58-3

CHIR-124

Catalog No. BCC3750----Order now to get a substantial discount!

Product Name & Size Price Stock
CHIR-124: 5mg $104 In Stock
CHIR-124: 10mg Please Inquire In Stock
CHIR-124: 20mg Please Inquire Please Inquire
CHIR-124: 50mg Please Inquire Please Inquire
CHIR-124: 100mg Please Inquire Please Inquire
CHIR-124: 200mg Please Inquire Please Inquire
CHIR-124: 500mg Please Inquire Please Inquire
CHIR-124: 1000mg Please Inquire Please Inquire
Related Products

Quality Control of CHIR-124

Number of papers citing our products

Chemical structure

CHIR-124

3D structure

Chemical Properties of CHIR-124

Cas No. 405168-58-3 SDF Download SDF
PubChem ID 11502647 Appearance Powder
Formula C23H22ClN5O M.Wt 419.91
Type of Compound N/A Storage Desiccate at -20°C
Solubility DMSO : 14 mg/mL (33.34 mM; Need ultrasonic and warming)
Chemical Name 4-[[(3S)-1-azabicyclo[2.2.2]octan-3-yl]amino]-6-chloro-3-(1,3-dihydrobenzimidazol-2-ylidene)quinolin-2-one
SMILES C1CN2CCC1C(C2)NC3=C4C=C(C=CC4=NC(=O)C3=C5NC6=CC=CC=C6N5)Cl
Standard InChIKey VBIIUHUSFOLTIU-LJQANCHMSA-N
Standard 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/h1-6,11,13,19,25-27H,7-10,12H2/t19-/m1/s1
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of CHIR-124

DescriptionCHIR-124 is a novel and potent inhibitor of Chk1 with an IC50 value of 0.3 nM.
TargetsChk1FLT3PDGFRGSK-3Fyn  
IC500.3 nM5.8 nM6.6 nM23.3 nM98.8 nM  

Protocol

Kinase Assay [1]
For the CHK1 assay, the kinase domain is expressed in Sf9 insect cells, and a biotinylated cdc25c peptide containing the consensus Chk1/Chk2 phosphorylation site (*)(biotin-[AHX]SGSGS*GLYRSPSMP-ENLNRPR[CONH2]) is used as the substrate. A dilution series of CHIR-124 is mixed with a kinase reaction buffer containing a final concentration of 30 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 2 mM DTT, 4 mM EDTA, 25 mM β-glycerophosphate, 5 mM MnCl2, 0.01% bovine serum albumin, 1.35 nM CHK1 kinase domain, 0.5 μM peptide substrate, and 1 μM unlabeled ATP, plus 5 nM 33P γ-labeled ATP (specific activity =2,000 Ci/mmol). Reactions and detection of the phosphate transfer are carried out by a radioactive method.

Animal Administration [1]
Severe combined immunodeficient mice harboring MDA-MD-435 tumor xenografts are randomized into the following treatment groups of 10: vehicle (captisol) alone, 5 mg/kg CPT-11, 10 mg/kg CHIR-124, 20 mg/kg CHIR-124, 5 mg/kg CPT-11 plus 10 mg/kg CHIR-124, or 5 mg/kg CPT-11 plus 20 mg/kg CHIR-124. Treatment is initiated on the day after randomization (day 1). CPT-11 is given i.p. daily (four times daily) ×5 on days 1 to 5, whereas CHIR-124 is given orally four times daily ×6 on days 2 to 7 in captisol. Percent tumor growth inhibition is defined as % T/C, where T = the treatment group mean, and C = the control group mean. In a similar study, tumors harvested from mice sacrificed on day 4 of treatment are examined for apoptosis by terminal deoxynucleotidyl transferase-mediated nick-end labeling staining and for mitotic index by immunofluorescence labeling with phospho-histone H3 antibody.

References:
[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.

CHIR-124 Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

CHIR-124 Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of CHIR-124

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.3815 mL 11.9073 mL 23.8146 mL 47.6293 mL 59.5366 mL
5 mM 0.4763 mL 2.3815 mL 4.7629 mL 9.5259 mL 11.9073 mL
10 mM 0.2381 mL 1.1907 mL 2.3815 mL 4.7629 mL 5.9537 mL
50 mM 0.0476 mL 0.2381 mL 0.4763 mL 0.9526 mL 1.1907 mL
100 mM 0.0238 mL 0.1191 mL 0.2381 mL 0.4763 mL 0.5954 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on CHIR-124

CHIR-124, a selective inhibitor, inhibits Chk1 with IC50 value of 0.3nM 2,000-fold more potently than Chk2 with IC50 value of 0.7μM. CHIR-124 also potently targets other kinases such as PDGFR with IC50 value of 6.6nM and FLT3 with IC50 value of 5.8nM [1].

CHIR-124 abrogates the S and G2-M checkpoints induced by topoisomerase I poisons and selectively sensitizes tumors lacking p53 function to undergo mitotic death. In addition, CHIR-124 enhances the antitumor effect of irinotecan in tumor xenografts by inhibiting the G2-M checkpoint and inducing apoptosis.

In vitro, the effect of a matrix of camptothecin and CHIR-124 combinations in a number of human cancer cell lines, including breast carcinoma (MDA-MB-231and MDAMB-435) and colon carcinoma (SW-620 and Colo205), all of which are mutant for p53. When cells were simultaneously exposed to a matrix of different concentration combinations of CHIR-124 and SN-38 for 48 h, significant synergy or >10% deviation from additivity was observed in the concentration ranges of ≥4.2×108 mol/L for SN-38 and≥ 6.0×108 mol/L for CHIR-124. Compared to IR alone, the number of mitotic cells increased dramatically in p53-/- HCT116 cells after concomitant Chir-124 exposure, while no such effect was observed in p53-sufficient WT HCT116 cells. Chir-124 was able to radiosensitize HCT116 cells that lack checkpoint kinase-2 (CHK2) or that were deficient for the spindle checkpoint protein Mad2. Additionally, Chir-124 could radiosensitize tetraploid cell lines, which were resistant to DNA damaging agents. Radiosensitization mediated by Chir-124 is greatly influenced by the p53 and cell cycle checkpoint system [1, 2].

In vivo, severe combined immunodeficient mice harboring MDA-MD-435 tumor xenografts were randomized into the treatment of 10 mg/kg CHIR-124, 20 mg/kg CHIR-124, 10 mg/kg CHIR-124 with 5 mg/kg CPT-11, or 20 mg/kg CHIR-124 with 5 mg/kg CPT-11. CPT-11 was given i.p. four times daily ×5 on days 1 to 5, while CHIR-124 was given orally four times daily ×6 on days 2 to 7 in captisol. Tumors harvested from mice sacrificed on day 4 of treatment were examined for apoptosis by terminal deoxynucleotidyl transferase-mediated nick-end labeling staining and for mitotic index by immunofluorescence labeling with phospho-histone H3 antibody in a similar study [1].

References:
[1]. Tse AN, Rendahl KG, Sheikh T, et al. CHIR-124, a novel potent inhibitor of Chk1, potentiates the cytotoxicity of topoisomerase I poisons in vitro and in vivo. Clinical Cancer Research, 2007, 13(2): 591-602.
[2]. Tao YG, Leteur C, Yang CY, et al. Radiosensitization by Chir-124, a selective CHK1 inhibitor Effects of p53 and cell cycle checkpoints. Cell Cycle, 2007, 8(8): 1196-1205.

Featured Products
New Products
  • Dovitinib (TKI-258, CHIR-258)

    Catalog No.:BCC1169
    CAS No.:405169-16-6
  • NFPS

    Catalog No.:BCC7484
    CAS No.:405225-21-0
  • Dadahol A

    Catalog No.:BCN5457
    CAS No.:405281-76-7
  • Cyclapolin 9

    Catalog No.:BCC7571
    CAS No.:40533-25-3
  • SB590885

    Catalog No.:BCC4392
    CAS No.:405554-55-4
  • GW3965

    Catalog No.:BCC1612
    CAS No.:405911-09-3
  • GW3965 HCl

    Catalog No.:BCC3790
    CAS No.:405911-17-3
  • C34

    Catalog No.:BCC5603
    CAS No.:40592-88-9
  • Cirazoline hydrochloride

    Catalog No.:BCC6833
    CAS No.:40600-13-3
  • DMT-Cl

    Catalog No.:BCC2799
    CAS No.:40615-36-9
  • DMT-T

    Catalog No.:BCC2843
    CAS No.:40615-39-2
  • DSP-4

    Catalog No.:BCC7527
    CAS No.:40616-75-9
 

References on CHIR-124

Radiosensitization by Chir-124, a selective CHK1 inhibitor: effects of p53 and cell cycle checkpoints.[Pubmed:19305158]

Cell Cycle. 2009 Apr 15;8(8):1196-205.

Checkpoint kinase-1 (CHK1) is a key regulator of the DNA damage-elicited G(2)-M checkpoints. The aim of the present study was to investigate the effects of a selective CHK1 inhibitor, Chir124, on cell survival and cell cycle progression following ionizing radiation (IR). Treatment with CHIR-124 resulted in reduced clonogenic survival and abrogated the IR-induced G(2)-M arrest in a panel of isogenic HCT116 cell lines after IR. This radiosensitizing effect was relatively similar between p53(-/-) and p53-sufficient wild type (WT) HCT116 cells. However, the number of mitotic cells (as measured by assessing the phosphorylation of mitotic proteins) increased dramatically in p53(-/-) HCT116 cells after concomitant CHIR-124 exposure, compared to IR alone, while no such effect was observed in p53-sufficient WT HCT116 cells. In p53(-/-) cells, CHIR-124 treatment induced a marked accumulation of polyploid cells that were characterized by micronucleation or multinucleation. p21(-/-) HCT116 cells displayed a similar pattern of response as p53(-/-) cells. CHIR-124 was able to radiosensitize HCT116 cells that lack checkpoint kinase-2 (CHK2) or that were deficient for the spindle checkpoint protein Mad2. Finally, CHIR-124 could radiosensitize tetraploid cell lines, which were relatively resistant against DNA damaging agents. Altogether these results suggest that CHIR-124-mediated radiosensitization is profoundly influenced by the p53 and cell cycle checkpoint system.

CHIR-124, a novel potent inhibitor of Chk1, potentiates the cytotoxicity of topoisomerase I poisons in vitro and in vivo.[Pubmed:17255282]

Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):591-602.

PURPOSE: Chk1 kinase is a critical regulator of both S and G(2)-M phase cell cycle checkpoints in response to DNA damage. This study aimed to evaluate the biochemical, cellular, and antitumor effects of a novel Chk1 inhibitor, CHIR124. EXPERIMENTAL DESIGN: CHIR-124 was evaluated for its ability to abrogate cell cycle checkpoints, to potentiate cytotoxicity, and to inhibit Chk1-mediated signaling induced by topoisomerase I poisons in human tumor cell line and xenograft models. RESULTS: CHIR-124 is a quinolone-based small molecule 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 abrogates the SN-38-induced S and G(2)-M checkpoints and potentiates apoptosis in MDA-MD-435 breast cancer cells. The abrogation of the G(2)-M checkpoint and induction of apoptosis by CHIR-124 are enhanced by the loss of p53. We have also shown that CHIR-124 treatment can restore the level of cdc25A protein, which is normally targeted by Chk1 for degradation following DNA damage, indicating that Chk1 signaling is suppressed in the presence of CHIR-124. Finally, in an orthotopic breast cancer xenograft model, CHIR-124 potentiates the growth inhibitory effects of irinotecan by abrogating the G(2)-M checkpoint and increasing tumor apoptosis. CONCLUSIONS: CHIR-124 is a novel and potent Chk1 inhibitor with promising antitumor activities when used in combination with topoisomerase I poisons.

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.

Keywords:

CHIR-124,405168-58-3,Natural Products,Chk, buy CHIR-124 , CHIR-124 supplier , purchase CHIR-124 , CHIR-124 cost , CHIR-124 manufacturer , order CHIR-124 , high purity CHIR-124

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: