CHIR-124Chk1 inhibitor,novel and potent CAS# 405168-58-3 |
- TCS 359
Catalog No.:BCC1183
CAS No.:301305-73-7
- Amuvatinib (MP-470, HPK 56)
Catalog No.:BCC2258
CAS No.:850879-09-3
- MK-8776 (SCH-900776)
Catalog No.:BCC3817
CAS No.:891494-63-6
- Quizartinib (AC220)
Catalog No.:BCC2548
CAS No.:950769-58-1
- PF-477736
Catalog No.:BCC4421
CAS No.:952021-60-2
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
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. |
Description | CHIR-124 is a novel and potent inhibitor of Chk1 with an IC50 value of 0.3 nM. | ||||||
Targets | Chk1 | FLT3 | PDGFR | GSK-3 | Fyn | ||
IC50 | 0.3 nM | 5.8 nM | 6.6 nM | 23.3 nM | 98.8 nM |
CHIR-124 Dilution Calculator
CHIR-124 Molarity Calculator
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. |
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
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
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.
- Besifloxacin HCl
Catalog No.:BCC4764
CAS No.:405165-61-9
- Drechslerine D
Catalog No.:BCN7502
CAS No.:405157-88-2
- Drechslerine A
Catalog No.:BCN7561
CAS No.:405157-84-8
- Salubrinal
Catalog No.:BCC4843
CAS No.:405060-95-9
- 4'-Demethylpodophyllotoxin
Catalog No.:BCN2625
CAS No.:40505-27-9
- Z-Lys(Z)-OH
Catalog No.:BCC2762
CAS No.:405-39-0
- LAQ824 (NVP-LAQ824,Dacinostat)
Catalog No.:BCC2160
CAS No.:404951-53-7
- Panobinostat (LBH589)
Catalog No.:BCC3601
CAS No.:404950-80-7
- Ethyl ferulate
Catalog No.:BCN1257
CAS No.:4046-02-0
- Bursehernin
Catalog No.:BCN3040
CAS No.:40456-51-7
- Yatein
Catalog No.:BCN5456
CAS No.:40456-50-6
- Kaempferol-3-O-glucorhamnoside
Catalog No.:BCN2830
CAS No.:40437-72-7
- 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
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.