Inositol hexakisphosphate kinase (IP6K) participates in diverse cellular signaling pathways by generating the inositol pyrophosphate InsP7, a highly energetic molecule, from their precursor InsP6. The physiological in vivo role of IP6K has not been fully characterized. We identified a crucial role of IP6K in regulating plasma phosphate levels in vivo and aim to apply this finding to new therapeutics.

Research results demonstrated that IP6K-generated InsP7 has a pivotal role in facilitating cellular phosphate export. When IP6K is inhibited, intracellular InsP7 levels are decreased and cellular phosphate export to extra-cellular space is potently decreased, resulting in deceased plasma phosphate levels and increased intracellular ATP levels in mammals.

SCO-006, identified by SCOHIA researchers and collaborators, is an orally bioactive IP6K inhibitor with a drug like profile. In preclinical studies, administration of SCO-006 decreased intracellular InsP7, an its enzymatic product, and potently decreased plasma phosphate levels in rats and monkeys. In a hyperphosphatemia rat model with chronic kidney disease, SCO-006 improved hyperphosphatemia and improved kidney functions. Improvement in kidney function is likely a result of IP6K inhibition-induced increased ATP levels in the kidney.

Based on these findings, IP6K inhibition can serve as a differentiated novel strategy to treat hyperphosphatemia and associated diseases, including chronic kidney disease, and SCO-006 has a potential to become a clinically applicable first-in-class IP6K inhibitor. SCOHIA is actively seeking a partner worldwide for further development and commercialization of SCO-006.

Indication

  • Hyperphosphatemia