BLU0588

• CAT Number: I040908
• CAS Number: 2810747-78-3
• Molecular Formula: C26H25N5O
• Molecular Weight: 423.51
• Purity: ≥95%
• Synonyms: N-[(1R,2R)-2-pyrrolidin-1-yl-2,3-dihydro-1H-inden-1-yl]-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyridine-3-carboxamide
• InChI: InChI=1S/C26H25N5O/c32-26(18-7-8-22(29-16-18)20-9-11-27-25-21(20)10-12-28-25)30-24-19-6-2-1-5-17(19)15-23(24)31-13-3-4-14-31/h1-2,5-12,16,23-24H,3-4,13-15H2,(H,27,28)(H,30,32)/t23-,24-/m1/s1
• InChIKey: YXSWSKFLTNJZEO-DNQXCXABSA-N
• SMILES: C1CCN(C1)C2CC3=CC=CC=C3C2NC(=O)C4=CN=C(C=C4)C5=C6C=CNC6=NC=C5

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[1].
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].

Reference

[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.