Discovery and Optimization of LATS1 and LATS2 Kinase Inhibitors for Use in Regenerative Medicine.

ABSTRACT: The Large Tumor Suppressor Kinases 1 and 2 (LATS1/2) are serine/threonine kinases that play an essential role in Hippo pathway activation and influence multiple physiological events ranging from organ growth to tissue regeneration. As a result, pharmacological inhibition of LATS1/2 represents a promising strategy for therapeutic intervention in multiple indications. Within, we present the discovery of potent and selective inhibitors of the kinases LATS1 and LATS2. Using a scaffold hopping strategy from the reported AKT inhibitor AT-7867 (1) we pursued a series of structure activity relationship (SAR) studies that dramatically improved potency versus LATS1 and LATS2, while concurrently improving kinome-wide selectivity. ADME properties were further optimized via introduction of conformation

SUBMITTER: Morris PJ 

PROVIDER: S-EPMC12406206 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature