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CCT245737

Catalog No. T7080 CAS 1489389-18-5

Synonyms: SRA737

CCT245737 (SRA737) is an orally active and selective Chk1 inhibitor (IC50: 1.3 nM); CCT245737 shows much less activity against Chk2 (IC50: 2440 nM).

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CCT245737, CAS 1489389-18-5

Pack Size	Availability	Price/USD
1 mg	In stock	$ 33.00
2 mg	In stock	$ 47.00
5 mg	In stock	$ 76.00
10 mg	In stock	$ 122.00
25 mg	In stock	$ 237.00
50 mg	In stock	$ 389.00
100 mg	In stock	$ 582.00
1 mL * 10 mM (in DMSO)	In stock	$ 84.00

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Purity: 99.69%

Purity: 99.23%

Purity: 98.06%

Biological Description

Chemical Properties

Storage & Solubility Information

Description	CCT245737 (SRA737) is an orally active and selective Chk1 inhibitor (IC50: 1.3 nM); CCT245737 shows much less activity against Chk2 (IC50: 2440 nM).
Targets&IC50	Chk1:1.4 nM (Cell-free)
In vitro	CCT245737 (10 μM) shows >80% inhibition of a panel of 124 kinases[1]. CCT245737 abrogates an etoposide-induced G2 checkpoint in HT29, SW620, MiaPaCa-2, and Calu6 cell lines, with IC50s ranging from 30 to 220 nM[2].
In vivo	CCT245737 (150 mg/kg, p.o) alone significantly inhibits tumor growth in an Eμ-Myc mouse model of human B-cell lymphocytic leukemia[2]. CCT245737 (150 mg/kg, p.o.) inhibits tumor growth in combination with gemcitabine (100 mg/kg i.v.) in HT29 colon cancer xenografts. CCT245737 (300 mg/kg, p.o.) also inhibits the gemcitabine (60 mg/kg, i.v.) induced pSer296 CHK1 autophosphorylation at 24 h in SW620 human colon cancer xenografts[1].
Kinase Assay	Commercial in vitro 33P radiometric kinase assays is carried out against 124 human kinases using 10 μM CCT245737 at ATP concentrations corresponding to the kinase Km, ATP [2].
Cell Research	Cytotoxicity is determined as the drug concentration that gives 50% inhibition of tumour cell proliferation (GI50) using a 96 h Sulforhodamine B (SRB) assay. Inhibition of intracellular CHK1 activity is measured using a cell-based ELISA for the abrogation of an etoposide-induced G2 checkpoint (mitosis induction assay, MIA). The IC50 for G2 checkpoint abrogation (MIA) is determined in the presence of nocodazole using UCN01 as a positive control. The activity index (AI) is used as a measure of the compounds ability to induce mitosis relative to its toxicity (i.e., ratio of MIA IC50: 96 h SRB GI50). Routine potentiation studies are carried out using a fixed concentration (GI50) of either gemcitabine or SN38 in combination with a range of CCT245737 concentrations to determine the combination GI50 of CCT245737. The ability of CCT245737 to enhance gemcitabine or SN38 cell killing is expressed as a potentiation index (PI) equal to the ratio of the GI50 for CCT245737 alone versus the combination GI50 for CCT245737. PI values > 1 indicate the potentiation of the genotoxic activity. In addition, a series of experiments is carried out using fixed, non- or minimally toxic concentrations of CCT245737 (≤GI20) with a range of different concentrations of gemcitabine or SN38 to determine the extent to which CCT245737 enhances drug cytotoxicity compared with the genotoxic agent alone, i.e. conventional PI (ratio GI50 genotoxic alone: GI50 genotoxic combined with non-toxic CCT245737 concentration, Con PI)[2].
Animal Research	Human HT29 colorectal carcinoma cells are injected s.c into the flanks of female NCr athymic mice 6-8 weeks of age. Dosing commenced 5 days after transplantation when tumours reach a mean diameter of 5.5 mm. Gemcitabine (100 mg/kg i.v.) is dosed in saline on days 0, 7 and 14 and compounds 4 (CCT245737) and 41 (150 mg/kg p.o.) in 10% DMSO 20% PEG 400, 5% Tween 80, 65% water, 24 and 48 h after each dose of gemcitabine. Tumours are measured and body weights recorded three times weekly. Animals are culled on an individual basis when tumours reach a predetermined humane endpoint (mean diameter <15 mm)[1].

Synonyms	SRA737
Molecular Weight	379.34
Formula	C16H16F3N7O
CAS No.	1489389-18-5

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

Ethanol: 5 mg/mL

H2O: Insoluble

DMSO: 50 mg/mL (131.81 mM)

References and Literature

1. Osborne JD, et al. Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737). J Med Chem. 2016 Jun 9;59(11):5221-37. 2. Walton MI, et al. The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eμ-MYC driven B-cell lymphoma. 3. Liang J, Niu Z, Yu X, et al. Counteracting Genome Instability by p53-dependent Mintosis[J]. bioRxiv. 2020. 4. Liang J, Niu Z, Zhang B, et al. Liang J, Niu Z, Zhang B, et al. p53-dependent elimination of aneuploid mitotic offspring by entosis[J]. Cell Death & Differentiation. 2020: 1-15.

Citations

1. Liang J, Niu Z, Zhang B, et al. p53-dependent elimination of aneuploid mitotic offspring by entosis. Cell Death & Differentiation. 2020: 1-15 2. Liang J, Niu Z, Zhang B, et al Liang J, Niu Z, Zhang B, et al. p53-dependent elimination of aneuploid mitotic offspring by entosis. Cell Death & Differentiation. 2020: 1-15.

Related compound libraries

This product is contained In the following compound libraries：

Anti-Cancer Clinical Compound Library Highly Selective Inhibitor Library Drug Repurposing Compound Library Anti-Cancer Active Compound Library Anti-Cancer Drug Library Inhibitor Library ReFRAME Related Library NO PAINS Compound Library Anti-Aging Compound Library Kinase Inhibitor Library

Related Products

Related compounds with same targets

Buddlejasaponin IV CCT241533 hydrochloride CCT241533 CHK1-IN-4 CHK-IN-1 Tuvusertib CHIR-124 BX-912

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Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.

Keywords

CCT245737 1489389-18-5 Cell Cycle/Checkpoint Chk CCT 245737 CCT-245737 SRA-737 Inhibitor inhibit SRA 737 Checkpoint Kinase (Chk) SRA737 inhibitor

Products are chemical reagents for research use only and are not intended for human use. We do not sell to patients.