In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
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 .
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 .
. 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.
. 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.
|Physical Appearance||A solid|
|Storage||Store at -20°C|
|Solubility||≥10.5mg/mL in DMSO|
|Shipping Condition||Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request|
|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.|
|Description||CHIR-124 is a novel and potent inhibitor of Chk1 with an IC50 value of 0.3 nM.|
|IC50||0.3 nM||5.8 nM||6.6 nM||23.3 nM||98.8 nM|