CCT245737 is a potent, selective and orally active checkpoint kinase 1 (CHK1) inhibitor, with IC50 values of 1.3 nM, 2440 nM and 30 nM for CHK1, CHK2 and G2 check point abrogation, respectively. CCT245737 (150 mg/kg, p.o) alone significantly inhibits tumor growth in an Eμ-Myc mouse model of human B-cell lymphocytic leukemia. 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.
Cell Experiment | |
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Cell lines | HT29, SW620, MiaPaCa-2 and Calu6 cell line |
Preparation 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 etoposide induced G2 checkpoint (mitosis induction assay, MIA). |
Concentrations | from 30 to 220nM |
Incubation time | 96 h |
Animal Experiment | |
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Animal models | BALB/c mice |
Formulation | vehicle for oral administration of CCT245737 was DPTW (10% DMSO, 20% PEG400, 5% Tween 80 and 65% water) |
Dosages | 10mg/kg (i.v.); 150mg/kg (p.o.) |
Administration | i.v. or p.o. administration |
Molecular Weight | 379.34 |
Formula | C16H16F3N7O |
CAS Number | 1489389-18-5 |
Solubility (25°C) | DMSO ≥ 45 mg/mL |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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