Recent Advances in ALK2 Inhibitors

Over the past few years, a greater diversity of chemotypes of ALK2 inhibitors have emerged. Some compounds had higher selectivity and those were modulated to ensure oral bioavailability and CNS penetration.

Please follow this LINK for the paper. Below are my personal notes for anyone who’s interested!

Two distinct chemotypes LDN193189 and LDN214117 were two of the early ALK2 inhibitors developed which presented good potency with their CNS penetration and good pharmacokinetics. With their ability to ablate signaling via phosphoSMAD downstream pathways, these two compounds were chosen by our lab for in vivo PK and efficacy studies to push forward for potential therapy for DIPG.

The paper “ALK2 inhibitors display beneficial effects in preclincal models of ACVR1 mutant diffuse intrinsic pontine glioma (Carvalho et al., 2019, Nature Communications Biology)” discusses the above two compounds in further detail! Please follow this LINK for my notes on this paper!