DS89002333 (C09-1126-055)

DS89002333 is an orally active and potent PRKACA inhibitor, with an IC 50 of 0.3 nM. DS89002333 shows good anti-tumor activity in an FL-HCC patient-derived xenograft model (expressing the DNAJB1-PRKACA fusion gene). DS89002333 can be used in study of fibrolamellar hepatocellular carcinoma (FL-HCC)In VitroDS89002333 (0.001, 0.01, 0.1, 1, 10 µM; 30 min) inhibits phosphorylation of CREB in a dose-dependent manner in NIH/3T3 cells (phosphorylation status of CREB as a marker of intracellular PRAKACA inhibitory activity). MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: NIH/3T3 cells Concentration: 0.001, 0.01, 0.1, 1, 10 µM Incubation Time: 30 min Result: Showed a dose-dependent decrease in phosphorylation of CREB, with an IC 50 of 50 nM.In VivoDS89002333 (12.5, 50 mg/kg; p.o.; twice daliy for 5 days) shows anti-tumor activity in an NIH/3T3-fusion allograft model . DS89002333 (3, 30 mg/kg; p.o.; twice daliy for 22 days) shows significant anti-tumor activity in FL-HCC PDX xenograft model . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female nude mice (NIH/3T3-fusion allograft model) . Dosage: 12.5, 50 mg/kg Administration: Oral administration, twice daliy for 5 days. Result: Exhibited anti-tumor activity without body weight loss. Animal Model: Female NOD SCID mice (FL-HCC PDX xenograft model) . Dosage: 3, 30 mg/kg Administration: Oral administration, twice daliy for 22 days. Result: Significant inhibited tumor in mice, and showed temporary body weight loss (at 30 mg/kg), but this resolved following continuous dosing.Form:SolidIC50& Target:PRKACA 0.3 nM (IC 50 ). Specifications and Purity: 99%. Molecular Formula: C22H20ClF2N3O3. Molecular Weight: 447.86.