DS89002333 is an orally active and potent PRKACA inhibitor, with an IC50 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)[1].
DS89002333 (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)[1].
Cell Viability Assay[1]
| Cell 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 IC50 of 50 nM. |
DS89002333 (12.5, 50 mg/kg; p.o.; twice daliy for 5 days) shows anti-tumor activity in an NIH/3T3-fusion allograft model[1].
DS89002333 (3, 30 mg/kg; p.o.; twice daliy for 22 days) shows significant anti-tumor activity in FL-HCC PDX xenograft model[1].
| Animal Model: | Female nude mice (NIH/3T3-fusion allograft model)[1]. |
| 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)[1]. |
| 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. |
[1]. Toyota A, et al. ovel protein kinase cAMP-Activated Catalytic Subunit Alpha (PRKACA) inhibitor shows anti-tumor activity in a fibrolamellar hepatocellular carcinoma model. Biochem Biops Res Commun. 2022 Sep 17;621:157-161.