OD36 hydrochloride (OD-36 hydrochloride) is a potent RIPK2 inhibitor with an IC50 of 5.3 nM.OD36 hydrochloride is a macrocyclic inhibitor that binds efficiently to the ATP pocket of the ALK2 kinase and effectively antagonizes mutant ALK2 signaling and osteogenic differentiation.OD36 hydrochloride targets ALK2. OD36 hydrochloride targets ALK2 with a KD of 37 nM.

ACVR1:37 nM (Kd), ACVR1:47 nM, RIPK2:5.3 nM, ALK2 (R206H):22 nM

OD36 hydrochloride inhibits ALK2 (IC50=47 nM) and ALK2 R206H （IC50=22 nM.[1]
OD36 hydrochloride exhibits a KD of 90 nM, demonstrating significant activity against ALK1. Additionally, it effectively acts as an antagonist against mutant ALK2 signaling and inhibits osteogenic differentiation.[2]
OD36 hydrochloride (0.1-1 μM; 24 h) effectively hinders the BMP-6 (50 ng/mL)-induced phosphorylation of Smad1/5 in KS483 cells. Moreover, when fibrodysplasia ossificans progressiva (FOP) endothelial colony-forming cells (ECFCs) are preincubated with 0.5 μM OD36 hydrochloride, it completely blocks the activation of Smad1/5 as well as the expression of the target genes ID-1 and ID-3 in response to activin A.[2]

OD36 (6.25 mg/kg; i.p.; once; C57BL/6 mice, muramyl dipeptide (MDP)-induced model of peritonitis) inhibited the recruitment of inflammatory cells to the peritoneum, specifically neutrophils and, to a lesser extent, lymphocytes. It decreased RIPK2-specific gene expression as well as inflammatory cytokine and chemokine gene expression, thereby alleviating inflammation in an acute peritonitis mice model.[3]