Activation of bone morphogenetic protein (BMP) type I receptors, also known as activin receptor-like kinases (ALK1-7), leads to the assembly of SMAD complexes, which translocate to the nucleus to induce transcriptional activation important for normal development and tissue repair. ML-347 is a 5-quinoline compound that inhibits ALK1 and ALK2 with IC50 values of 46 and 32 nM, respectively. It demonstrates >300-fold selectivity for ALK2 over ALK3, ALK6, and VEGF type 2 receptor (IC50s = 10.8, 9.8, and 19.7 μM, respectively) and is inactive at ALK4, ALK5, BMP type 2 receptors, TGF-β type 2 receptor, and AMPK. In a functional assay, ML-347 was shown to inhibit BMP4 signaling with an IC50 value of 152 nM.
