M4K2234

SKU: orb1982742

Description

M4K2234 is a potent and selective ALK2 inhibitor (IC50 = 5 nM) with >400-fold selectivity over ALK5. This chemical probe is a valuable tool for investigating BMP signaling mechanisms and studying diseases like fibrodysplasia ossificans progressiva (FOP) and certain cancers in both cellular and animal models.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 2421141-51-5
• MW: 462.56
• Purity: 99.99% (May vary between batches)
• Formula: C₂₇H₃₁FN₄O₂
• SMILES: O=C(N)C1=C(F)C=C(C=C1OC)C2=CN=CC(C3=CC=C(C=C3)N4CCN(CC4)C(C)C)=C2C
• Target: ALK
• Solubility: DMSO:80 mg/mL (172.95 mM)

Bioactivity

• Target IC50:
  ALK2:14 nM|ALK4:1660 nM|ALK3:168 nM|ALK1:7 nM|ALK5:1950 nM|ALK6:88 nM
• In Vivo:
  M4K2234 demonstrated favorable pharmacokinetic properties and notable brain permeability in in vivo mouse studies. In the pharmacokinetic analysis, the compound achieved excellent bioavailability following oral administration at a dose of 10 mg/kg in mice .
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• In Vitro:
  In the HEK293 cell model, M4K2234 at a concentration of 16 nM potently blocked BMP7-mediated reporter gene activation; in contrast, the inhibitory activity of this compound against CAGA-responsive reporter genes induced by activin A and TGF-β1 was significantly attenuated, with the inhibitory potency reduced by 50-fold and 150-fold, respectively . At the administration concentration ranging from 0.5 to 1 μM, M4K2234 exhibited distinct action specificity in HEK293T cells—it only targeted and inhibited the SMAD1/5/8 phosphorylation process triggered by BMP family ligands, whereas it exerted no obvious effect on SMAD2/3 phosphorylation induced by activin A or TGF-β1 . Enzyme kinetic assay results demonstrated that M4K2234 had strong inhibitory activity against ALK1 and ALK2, with the corresponding half-maximal inhibitory concentrations (IC₅₀) of 7 nM and 14 nM, respectively; it showed weak inhibitory effect on ALK6, with an IC₅₀ of 88 nM; and it had almost no inhibitory activity against ALK4/5, with an IC₅₀ greater than 10,000 nM .
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

M4K-2234, M4K 2234

Compound Identifiers

PubChem CID

155548898