BLU0588

BLU0588 (also known as BLU-0588) is a potent, selective, and orally active small-molecule inhibitor of the cAMP-dependent protein kinase catalytic subunit alpha (PRKACA), developed by Blueprint Medicines. It binds to the ATP-binding site of PRKACA with picomolar affinity, stabilizing the kinase in an open but ordered conformation and blocking its catalytic activity. BLU0588 has been investigated preclinically for the treatment of fibrolamellar carcinoma (FLC), a rare liver cancer driven by the DNAJB1-PRKACA gene fusion, where it has demonstrated significant tumor growth inhibition in patient-derived xenograft models. Additionally, it has shown protective effects in preclinical models of autosomal dominant polycystic kidney disease (ADPKD) by reducing cystogenesis [1], and has been studied as a potential agent to overcome PKA-mediated metformin resistance in head and neck squamous cell carcinoma (HNSCC).

Other names

N-((1R,2R)-2-(pyrrolidin-1-yl)-2,3-dihydro-1H-inden-1-yl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)nicotinamideN-[(1R,2R)-2,3-Dihydro-2-(1-pyrrolidinyl)-1H-inden-1-yl]-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-3-pyridinecarboxamide