Home Cell Cycle Chk inhibitor CCT245737 (SRA737) For research use only.

CCT245737 (SRA737)

Synonyms: PNT-737

CCT245737 (SRA737) is an orally active CHK1 inhibitor with The IC50 of 1.4 nM. It exhibits >1,000-fold selectivity against CHK2 and CDK1.

CCT245737 (SRA737) Chemical Structure

CCT245737 (SRA737) Chemical Structure

CAS No. 1489389-18-5

Purity & Quality Control

CCT245737 (SRA737) Related Products

Signaling Pathway

Chk Signaling Pathways

Chk Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HEK293 cells Antiproliferative assay 72 hrs Antiproliferative activity against human HEK293 cells after 72 hrs by MTS assay, GI50=1.387μM. 29684894
HT-29 cells Antiproliferative assay 72 hrs Antiproliferative activity against human HT-29 cells after 72 hrs by MTS assay, GI50=9.223μM. 29684894
Click to View More Cell Line Experimental Data

Biological Activity

Description CCT245737 (SRA737) is an orally active CHK1 inhibitor with The IC50 of 1.4 nM. It exhibits >1,000-fold selectivity against CHK2 and CDK1.
Targets
Chk1 [1]
(Cell-free assay)
1.4 nM
In vitro
In vitro

CCT245737 is a potent inhibitor of recombinant human CHK1 with IC50 of 1.4±0.3 nM (mean±SD, n = 3, EZ Reader II assay). There is > 1,000-fold selectivity for CHK1 versus the functionally important kinases CDK1 and CHK2 (IC50=1.26-2.44 and 9.03 μM, respectively), and at least a 90-fold selectivity against cross-reacting kinases such as ERK8, PKD1, RSK1 and 2. CCT245737 potently inhibits cellular CHK1 activity (IC50 30-220nM) and enhances SN38 cytotoxicity in multiple human tumor cell lines and human tumor xenograft models. It can abrogate an induced G2/M arrest. CCT245737 has high cell permeability, as measured by transport across a CaCo2 cell monolayer[1].
Cell Research Cell lines The colon tumor cell lines HT29 and SW620, the pancreatic cancer cell line MiaPaCa-2 and the non-small cell lung cancer Calu6 cell line
Concentrations --
Incubation Time 96 h
Method

Cytotoxicity is determined as the drug concentration that gave 50% inhibition of tumor cell proliferation (GI50) using a 96h (i.e. 4-doublings) Sulforhodamine B (SRB) assay. Inhibition of intracellular CHK1 activity is measured using a cell based ELISA for the abrogation of an induced G2 checkpoint (mitosis induction assay, MIA).
In Vivo
In vivo

Mouse oral bioavailability is complete (100%) with extensive tumor exposure. CCT245737 shows significant single-agent activity against a MYC-driven mouse model of B-cell lymphoma. An i.v. dose of 10mg/kg CCT245737 into BALB/c mice gives a peak plasma concentration of 4μmol/L, with a half-life of 2.86h, an AUC0-∞ of 9.96μmol.h/L, a plasma clearance of 2.1L/h/kg and a large volume of distribution (0.19L). The equivalent oral dose gave an almost identical profile with an AUC0-∞ of 10.4μmol.h/L showing complete oral bioavailability (F = 105%). In a word, CCT245737 shows complete oral bioavailability with linear pharmacokinetics and high tumor/plasma ratios consistent with extensive tumor exposure. Adequate CCT245737 tumor drug exposure takes a significant antitumor activity[1].
Animal Research Animal Models BALB/c mice
Dosages 10mg/kg(i.v.); 150mg/kg(p.o.)
Administration i.v. or p.o. administration
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02797964 Completed
Advanced Solid Tumors or Non-Hodgkin''s Lymphoma (NHL)
Sierra Oncology LLC - a GSK company
 July 2016 Phase 1|Phase 2
NCT02797977 Completed
Advanced Solid Tumors
Sierra Oncology LLC - a GSK company
 July 2016 Phase 1|Phase 2

Chemical Information & Solubility

Molecular Weight 379.34 Formula

C16H16F3N7O
CAS No. 1489389-18-5 SDF --
Smiles C1COC(CN1)CNC2=CC(=NC=C2C(F)(F)F)NC3=NC=C(N=C3)C#N
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 76 mg/mL ( (200.34 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


Molecular Weight Calculator

In vivo
Batch:

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In vivo Formulation Calculator

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In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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