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説明

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. K02288 is a 2-aminopyridine-based inhibitor of ALK1 and ALK2 with IC50 values of 1.8 and 1.1 nM, respectively. It is less selective for ALK3, 4, 5, and 6 subtypes and the type II BMP receptor ActRIIA, demonstrating IC50 values of 34.4, 302, 321, 6.4, and 220 nM, respectively. K02288 can prevent BMP4-induced SMAD1/5/8 pathway activation in vitro (IC50 = 100 nM) without affecting TGF-β signaling. Furthermore, at 8-10 μM, K02288 has been used to induce the dorsalization of zebrafish embryos. Through specific inhibition of BMP signaling, this compound can be used to research stem cell biology and disease models of musculoskeletal dysplasia and cancer.