CCT-245737

SKU: orb1226194

Description

A highly potent, selective, ATP-competitive inhibitor of Chk1 with IC50 of 1.3 nM; weak inhibition on Chk2 (IC50=2440 nM); inhibits genotoxic-induced CHK1 activity (pS296 CHK1) and cell cycle arrest (pY15 CDK1) both in vitro and in human tumor xenografts; showes significant single-agent activity against a MYC-driven mouse model of B-cell lymphoma; orally active.Solid Tumors Phase 1 Clinical(In Vitro):CCT245737 (10 μM) shows >80% inhibition of a panel of 124 kinases, including ERK8, PKD1, RSK2 and RSK1 with IC50s of 130, 298, 361 and 362 nM. CCT245737 abrogates an VP-16-induced G2 checkpoint in HT29, SW620, MiaPaCa-2, and Calu6 cell lines, with IC50s ranging from 30 to 220 nM.(In Vivo):CCT245737 (150 mg/kg p.o.) inhibits tumor growth in combination with LY 188011 (100 mg/kg iv) in HT29 colon cancer xenografts. CCT245737 (300 mg/kg, p.o.) also inhibits the LY 188011 (60 mg/kg iv) induced pSer296 CHK1 autophosphorylation at 24 h in SW620 human colon cancer xenografts. CCT245737 (150 mg/kg, p.o) alone significantly inhibits tumor growth in an Eμ-Myc mouse model of human B-cell lymphocytic leukemia.

Key Properties

• CAS Number: 1489389-18-5
• MW: 379.3398
• Purity: >98% (HPLC)
• Formula: C₁₆H₁₆F₃N₇O
• SMILES: N#CC1=NC=C(NC2=NC=C(C(F)(F)F)C(NC[C@H]3CNCCO3)=C2)N=C1
• Target: Chk
• Solubility: DMSO: ≥ 32 mg/mL

Bioactivity

• In Vivo:
  CCT245737 (150 mg/kg p.o.) inhibits tumor growth in combination with LY 188011 (100 mg/kg iv) in HT29 colon cancer xenografts. CCT245737 (300 mg/kg, p.o.) also inhibits the LY 188011 (60 mg/kg iv) induced pSer296 CHK1 autophosphorylation at 24 h in SW620 human colon cancer xenografts. CCT245737 (150 mg/kg, p. o) alone significantly inhibits tumor growth in an Eμ-Myc mouse model of human B-cell lymphocytic leukemia.
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• In Vitro:
  CCT245737 (10 μM) shows > 80% inhibition of a panel of 124 kinases, including ERK8, PKD1, RSK2 and RSK1 with IC50s of 130, 298, 361 and 362 nM. CCT245737 abrogates an VP-16-induced G2 checkpoint in HT29, SW620, MiaPaCa-2, and Calu6 cell lines, with IC50s ranging from 30 to 220 nM.
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

SRA-737 | SRA737 | SRA 737 | CCT245737 | CCT 245737

Quick Database Links

Gene Symbol

Chk