ALK2 Inhibitor

Dorsomorphin (BML-275) is a selective and ATP-competitive AMPK inhibitor (K_i=109 nM in the absence of AMP). Dorsomorphin (BML-275) selectively inhibits BMP type I receptors ALK2, ALK3, and ALK6. Dorsomorphin can reverse autophagy activation and anti-inflammatory effect of Urolithin A (HY-100599).

LDN193189 (DM-3189) is a potent selective BMP type I receptor (BMP I) inhibitor. LDN193189 efficiently inhibits transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC₅₀ values of 5 nM and 30 nM, respectively. LDN193189 can be used for the research of bone morphogenetic protein signalling, such as fibrodysplasia ossificans progressiva.

Dorsomorphin (Compound C) dihydrochloride is a potent, selective and ATP-competitive AMPK inhibitor, with a K_i of 109 nM. Dorsomorphin dihydrochloride inhibits BMP pathway by targeting the type I receptors ALK2, ALK3, and ALK6. Dorsomorphin dihydrochloride can reverse autophagy activation and anti-inflammatory effect of Urolithin A (HY-100599).

LDN193189 (DM-3189) Tetrahydrochloride is a potent selective BMP type I receptor (BMP I) inhibitor. LDN193189 efficiently inhibits transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC₅₀ values of 5 nM and 30 nM, respectively. LDN193189 can be used for the research of bone morphogenetic protein signalling, such as fibrodysplasia ossificans progressiva.

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) .

RKER-216 is a human monoclonal IgG antibody inhibitor targeting ALK2 with a K_D of 58.7 pM. RKER-216 reduces hepcidin transcription in Hep3B.RKER-216 competes with BMP ligands for binding to the extracellular domain of ALK2, thereby inhibiting BMP-SMAD signal. RKER-216 mobilizes tissue iron effectively in inflammatory conditions. RKER-216 improves microcytic anemia in a dose-dependent manner by inhibiting SMAD signaling to reduce hepcidin and promote iron absorption and utilization in vivo. RKER-216 can be used for research on anemia of inflammation.

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.

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.

Zilurgisertib (INCB-000928; NBU-928) is a selective ALK2 inhibitor with an IC₅₀ value of 15 nM. Zilurgisertib inhibits SMAD1/5 phosphorylation with an IC₅₀ value of 63 nM. Zilurgisertib inhibits hepcidin production and improve anemia. Zilurgisertib can be used in melanoma research.

OD36 is a RIPK2 inhibitor with an IC₅₀ of 5.3 nM. OD36 is a macrocyclic inhibitor with potent binding to the ALK2 kinase ATP pocket. OD36 shows ALK2-directed activity with K_Ds of 37 nM.

ALK2-IN-2 is an orally active and selective inhibitor of ALK2 (ACVR1), with an IC₅₀ value of 9 nM, and over 700-fold selectivity against ALK3. ALK2-IN-2 can inhibit oxidative stress and protect endothelial cells.

Itacnosertib (TP-0184) is the inhibitor for FLT3, ACVR1 (ALK2, IC₅₀=8 nM) and JAK2 (IC₅₀=8540 nM). Itacnosertib exhibits anti-leukemic activity.

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

M4K2009 is an orally active, blood-brain barrier permeable type I ALK2 inhibitor, with an IC₅₀ value of 8-13 nM against human ALK2. M4K2009 exhibits moderate off-target inhibitory activity against hERG potassium channels (Potassium Channel), with an IC₅₀ of 8 μM against the human channel. M4K2009 can be used in studies related to diffuse intrinsic pontine glioma.

KER047 (ALK2-IN-4) is a potent activin receptor-like kinase-2 (ALK2) inhibitor. KER047 can be used for the research of metabolic disease, such as fibrodysplasia ossificans progressiva (FOP).

Itacnosertib hydrochloride (TP-0184 hydrochloride) is the inhibitor for FLT3, ACVR1 (ALK2, IC₅₀=8 nM) and JAK2 (IC₅₀=8540 nM). Itacnosertib hydrochloride exhibits anti-leukemic activity.

KER047 succinate (ALK2-IN-4 succinate) is a potent activin receptor-like kinase-2 (ALK2) inhibitor. KER047 succinate can be used for the research of metabolic disease, such as fibrodysplasia ossificans progressiva (FOP).

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.