BLU0588 is an orally active, potent and selective PRKACA (protein kinase cAMP-activated catalytic subunit alpha) kinase inhibitor, with an IC50 of 1 nM and dissociation constant (Kd) of 4 nM. BLU0588 can be used for fibrolamellar carcinoma (FLC) research.
BLU0588 (1.5 μM, 1 day or 14 days) reverses a FLC-specific gene signature, leading to downregulation of genes that are overexpressed in FLC (CPS1 and G6PC, top) and upregulation of genes that are underexpressed in FLC[1].BLU0588 (0-312.5 nM) reduces pVASP in FLC PDX cells in a dose-dependent manner[1].
BLU0588 (30-75 mg/kg, orally, once) can inhibit PRKACA, effectively inhibits downstream signaling of PRKACA, phosphorylated VASP levels returns to baseline levels by 24 hours[1]. The highest tolerated dose of BLU0588 for more than 3 weeks of continuous dosing was established as 30 mg/kg QD in mice[1].BLU0588 (30 mg/kg, orally, once daily, 34 days) can inhibits tumor growth in mice[1].
References:
[1]. Stefanie S. Schalm, et al. Evaluation of Protein Kinase cAMP-Activated Catalytic Subunit Alpha as a Therapeutic Target for Fibrolamellar Carcinoma. Gastro Hep Advances. Volume 2, Issue 3, 2023, Pages 307-321.