Inhibition of ALK2 with bicyclic pyridyllactams
Michael R Witten1, Liangxing Wu1, Cheng-Tsung Lai1
1Incyte Research Institute, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE 19803, United States.
Abstract:
Activin receptor-like kinase 2 (ALK2) has been implicated as a key target in multiple rare diseases. Herein, we describe the design of a novel bicyclic lactam series of potent and selective ALK2 inhibitors. This manuscript details an improvement in potency of two orders of magnitude from the initial bicyclic structure as well as a two-fold improvement in cellular potency from the original monocyclic inhibitor. Furthermore, we provide a detailed strategy for progressing this project in the future.
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