ALK1 Inhibitor

LDN-214117 is an orally active ALK2 inhibitor with well-tolerated and good brain penetration. LDN-214117 has a high selectivity and low cytotoxicity for ALK2 with an IC₅₀ value of 24 nM. LDN-214117 also is a specific bone morphogenetic proteins (BMPs) signaling inhibitor and has relatively selective inhibition for BMP6 with an IC₅₀ value of 100 nM. LDN-214117 can be used for the research of fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine glioma (DIPG) .

LDN-212854 is a bone morphogenetic protein (BMP) inhibitor that potently inhibits ALK2 (IC₅₀: 1.3 nM). LDN-212854 also inhibits ALK1 (IC₅₀: 2.40 nM). LDN-212854 can be used in the research of fibrodysplasia ossificans progressive and cancers, such as hepatocellular carcinoma (HCC).

ML347 (LDN193719) is a highly selective ALK1/ALK2 inhibitor. ML347 has IC₅₀ values of 46 and 32 nM against ALK1 and ALK2, respectively, >300-fold selective over ALK3. ML347 block the phosphorylation of Smad1/5 by TGF-β1.

Fidrisertib (BLU-782) is the orally active inhibitor for activin receptor-like kinase 2 (ALK2) that inhibits ALK2^R206H, ALK2, ALK1, ALK6, ALK3, ALK4, TGFβR2 and ALK5 with IC₅₀s of 0.2, 0.6, 3, 24, 45, 65, 67 and 155 nM, respectively.

AZ12799734 is a selective, orally active TGFBR1 kinase inhibitor with an IC₅₀ of 47 nM. AZ12799734 is also a pan BMP and TGFβ inhibitor.

HM-279 is a potent and orally active ALK5 inhibitor with an IC₅₀ of 4.7 nM. HM-279 shows cross-reactivity with ALK7 (IC₅₀ = 6.8 nM), but HM-279 has fair to good selectivity against other TGF-β receptor family kinases, with 4.5-693-fold selectivity. HM-279 demonstrates antitumor activity in vivo through CD8⁺ T cell immunity. HM-279 can be used for the research of colon cancer.

CDD-2789 is a potent and selective ALK2 inhibitor with an IC₅₀ 0.54 μM and a K_d of 2.1 nM, respectively. CDD-2789 exhibits >120-fold selectivity over ALK3/5/6. CDD-2789 reduces activin A- and BMP2-induced SMAD1/5 phosphorylation in fibroblasts. CDD-2789 can be used for ALK2-related cancer research.

MU1700, a chemical probe, is an orally active and potent ALK1/2 inhibitor with IC₅₀s of 13 nM and 6 nM, respectively. MU1700 shows cell membrane permeability and high brain permeability.