[CAS NO. 1489389-18-5] CCT245737
PRODUCTS SPECIFICATIONS [1489389-18-5]
DESCRIPTION [1489389-18-5]
Overview
| MDL | MFCD30489721 |
|---|---|
| Molecular Weight | 379.34 |
| Molecular Formula | C16H16F3N7O |
| SMILES | FC(F)(F)C(C=NC(NC1=CN=C(C#N)C=N1)=C2)=C2NC[C@H]3CNCCO3 |
Summary
CCT245737 is an orally active and seletive Chk1 inhibitor, with an IC 50 of 1.3 nM.
IC50 & Target
|
Chk1 1.3 nM (IC 50 ) |
Chk2 2440 nM (IC 50 ) |
ERK8 130 nM (IC 50 ) |
PKD1 298 nM (IC 50 ) |
RSK2 361 nM (IC 50 ) |
RSK1 362 nM (IC 50 ) |
FLT3 582 nM (IC 50 ) |
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MARK3 698 nM (IC 50 ) |
NUAK1 711 nM (IC 50 ) |
CLK2 1370 nM (IC 50 ) |
BRSK1 1660 nM (IC 50 ) |
AMPK 2970 nM (IC 50 ) |
PHK 3470 nM (IC 50 ) |
CDK2/CyclA 3850 nM (IC 50 ) |
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CDK1/CyclB 9030 nM (IC 50 ) |
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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 IC 50 s of 130, 298, 361 and 362 nM [1] . CCT245737 abrogates an VP-16-induced G2 checkpoint in HT29, SW620, MiaPaCa-2, and Calu6 cell lines, with IC 50 s ranging from 30 to 220 nM [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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 [1] . CCT245737 (150 mg/kg, p.o) alone significantly inhibits tumor growth in an Eμ-Myc mouse model of human B-cell lymphocytic leukemia [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 32 mg/mL ( 84.36 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.6362 mL | 13.1808 mL | 26.3616 mL |
| 5 mM | 0.5272 mL | 2.6362 mL | 5.2723 mL |
| 10 mM | 0.2636 mL | 1.3181 mL | 2.6362 mL |
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1.
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Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (6.59 mM); Clear solution
References
- [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. 201
- [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.