ALK2
ALK2, also known as ACVR1, is a type I serine/threonine kinase receptor of the transforming growth factor-β (TGF-β) superfamily that functions as a bona fide bone morphogenetic protein (BMP) receptor and transduces osteogenic signaling through BMP-dependent pathways[1][2]. Mechanistically, ALK2 forms ligand-induced receptor complexes that activate downstream SMAD1/5/8 signaling, thereby regulating cellular differentiation, skeletal development, and chondrogenic processes[3][4]. ALK2 has a central role in BMP receptor biology, and functional annotation of ACVR1 has established its importance in both physiological signaling and disease-associated pathway dysregulation[2][5]. In disease settings, gain-of-function mutations in ACVR1/ALK2 cause aberrant activation of BMP signaling and are strongly associated with fibrodysplasia ossificans progressiva (FOP), a disorder characterized by heterotopic ossification[2][6][7]. Activating ACVR1 mutations have also been identified in diffuse intrinsic pontine glioma (DIPG), extending the pathological relevance of ALK2 beyond skeletal disease[2][5]. Compared with related BMP type I receptors, ALK2 exhibits distinct ligand responsiveness and signaling regulation, including activation by specific BMP ligands and context-dependent interactions with activin receptor complexes that influence SMAD1/5/8 activity[4]. For experimental applications, selective inhibition of ALK2 signaling has become an important strategy for investigating pathological BMP pathway activation, and compounds such as LDN-212854 have been developed to achieve ALK2-biased inhibition with improved receptor selectivity[8]. Consequently, ALK2 serves as a critical molecular target for mechanistic studies of BMP signaling and for preclinical evaluation of therapeutic approaches directed at ACVR1-driven diseases[2][8].
References:
- [1]. Katagiri T, et al. Accumulated Knowledge of Activin Receptor-Like Kinase 2 (ALK2)/Activin A Receptor, Type 1 (ACVR1) as a Target for Human Disorders. Biomedicines. 2021 Jun 26;9(7):736. [Content Brief]
- [2]. Ketter-Katz H, et al. Vision in chameleons-A model for non-mammalian vertebrates. Semin Cell Dev Biol. 2020 Oct;106:94-105. [Content Brief]
- [3]. Zhang D, et al. ALK2 functions as a BMP type I receptor and induces Indian hedgehog in chondrocytes during skeletal development. J Bone Miner Res. 2003 Sep;18(9):1593-604. [Content Brief]
- [4]. Olsen OE, et al. BMPR2 inhibits activin and BMP signaling via wild-type ALK2. J Cell Sci. 2018 Jun 11;131(11):jcs213512. [Content Brief]
- [5]. Valer JA, et al. ACVR1 Function in Health and Disease. Cells. 2019 Oct 31;8(11):1366. [Content Brief]
- [6]. Shore EM, et al. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet. 2006 May;38(5):525-7. [Content Brief]
- [7]. Le VQ, et al. Hyperactive BMP signaling induced by ALK2(R206H) requires type II receptor function in a Drosophila model for classic fibrodysplasia ossificans progressiva. Dev Dyn. 2012 Jan;241(1):200-14. [Content Brief]
- [8]. Mohedas AH, et al. Development of an ALK2-biased BMP type I receptor kinase inhibitor. ACS Chem Biol. 2013;8(6):1291-302. [Content Brief]
All Product Categories
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ALK2 Related Products (31)
Related Products (31)
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Recombinant Proteins (14)
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M4K2281
0 ImagesCat. No.: HY-161376CAS No.: 3034840-19-9M4K2281 is a selecitve inhibitor for activin receptor-like kinase-2 (ALK2) with an IC50 of 2 nM. M4K2281 exhibits a moderate blood brain permeability with a brain to plasma ratio of 3.7 at 4h.
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ALK5-IN-33
0 ImagesCat. No.: HY-151283CAS No.: 2785430-89-7ALK5-IN-33 (Compound EX-10) is a selective, orally active ALK-5 inhibitor with an IC50 ≤10 nM.
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RKER-216
0 ImagesCat. No.: HY-P991855RKER-216 is a human monoclonal IgG antibody inhibitor targeting ALK2 with a KD 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.
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CDD-1115
0 ImagesCat. No.: HY-171248CAS No.: 3034215-86-3CDD-1115 is a BMPR2 serine/threonine kinase inhibitor with an IC50 of 1.8 nM against human BMPR2 kinase. CDD-1115 selectively inhibits the catalytic activity of BMPR2, and shows weak inhibitory effects on ALK1 and ALK2.
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ALK5-IN-25
0 ImagesCat. No.: HY-151270CAS No.: 2785430-81-9ALK5-IN-25 (compound EX-02) is a potent ALK-5 inhibitor with an IC50 ≤10 nM.ALK5-IN-25 also inhibits ALK-2 (selectivity ALK2/ALK5≤10). ALK5-IN-25 can be used for the research of cancer.
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MU1700
0 ImagesCat. No.: HY-148246CAS No.: 3055312-41-6MU1700, 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.
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ALK5-IN-27
0 ImagesCat. No.: HY-151273CAS No.: 2785430-83-1ALK5-IN-27 (Compound EX-04) is a potent ALK-5 inhibitor with an IC50 ≤10 nM. ALK5-IN-27 also inhibits ALK-2 (selectivity ALK2/ALK5 ≤10).
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M4K2306
0 ImagesCat. No.: HY-161377CAS No.: 3034840-25-7M4K2306 is a selective inhibitor for activin receptor-like kinase-2 (ALK2) with an IC50 of 7 nM. M4K2306 is blood brain permeable with a brain to plasma ratio of 75.6.
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ALK2-IN-6
0 ImagesCat. No.: HY-176941CAS No.: 2600795-23-9
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M4K2009 hydrochloride
0 ImagesCat. No.: HY-149591ACAS No.: 2772902-12-0M4K2009 hydrochloride is an orally active, blood-brain barrier permeable type I ALK2 inhibitor, with an IC50 value of 8-13 nM against human ALK2. M4K2009 hydrochloride exhibits moderate off-target inhibitory activity against hERG potassium channels (Potassium Channel), with an IC50 of 8 μM against the human channel. M4K2009 hydrochloride can be used in studies related to diffuse intrinsic pontine glioma.
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