The structures of salt-inducible kinase 3 in complex with inhibitors reveal determinants for binding and selectivity.

ABSTRACT: The salt-inducible kinases (SIKs) 1 to 3, belonging to the AMPK-related kinase family, serve as master regulators orchestrating a diverse set of physiological processes such as metabolism, bone formation, immune response, oncogenesis, and cardiac rhythm. Owing to its key regulatory role, the SIK kinases have emerged as compelling targets for pharmacological intervention across a diverse set of indications. Therefore, there is interest in developing SIK inhibitors with defined selectivity profiles both to further dissect the downstream biology and for treating disease. However, despite a large pharmaceutical interest in the SIKs, experimental structures of SIK kinases are scarce. This is likely due to the challenges associated with the generation of proteins suitable for structural studies.

SUBMITTER: Oster L 

PROVIDER: S-EPMC11061224 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature