| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
IC50: 5 nM (ALK2 WT), 3 nM (ALK2 G328V), 6 nM (ALK2 R206H), 6 nM (ALK2 R258G), 2144 nM (ALK5)[1]
M4K2234 targets ALK1 (activin receptor-like kinase 1) and ALK2 (activin receptor-like kinase 2), which are type I receptors of the TGF-beta superfamily involved in BMP signaling. It is highly selective for ALK1 (IC50 = 7 nM) and ALK2 (IC50 = 14 nM) over ALK3 (168 nM), ALK4 (1,660 nM), ALK5 (1,950 nM), ALK6 (88 nM), and 30 additional kinases at 1 uM. |
|---|---|
| ln Vitro |
M4K2234 (0-5 μM) exhibits inhibitory effects against ALK2 mutants associated to DIPG with IC50s of 5, 3, 6 and 6 nM for WT, G328V, R206H and R258G, respectively[1].
M4K2234 inhibits BMP7-stimulated reporter gene activity with an IC50 of 16 nM. It specifically blocks BMP signaling by inhibiting the phosphorylation of SMAD1/5/8. This compound is used as a chemical probe for ALK1 and ALK2 protein kinases and can be used for the investigation of ALK1/2-mediated biological processes and related diseases such as diffuse midline glioma (DMG) and fibrodysplasia ossificans progressiva (FOP). |
| ln Vivo |
1.19 M4K2234's Pharmacokinetic Properties in Mice [1]. Mice PO 3 mg/kg t1/2(h) 2.61 1650 AUCinf(ng·h/mL) 1650 Cmax(ng/mL)
Dedicated in vivo efficacy studies for M4K2234 are not detailed. As an orally active, highly selective inhibitor of ALK1 and ALK2, it is expected to show efficacy in mouse models of diffuse midline glioma (DMG) or fibrodysplasia ossificans progressiva (FOP), where aberrant BMP signaling drives pathology. |
| Enzyme Assay |
A biochemical ALK1 and ALK2 kinase inhibition assay is performed using purified recombinant ALK1 or ALK2 enzyme. Increasing concentrations of M4K2234 are pre-incubated with the enzyme and ATP. A peptide substrate is added, and phosphorylation is measured using a time-resolved fluorescence resonance energy transfer (TR-FRET) or radiometric method to determine IC50 values (7 nM for ALK1, 14 nM for ALK2). Selectivity is assessed against a panel of other kinases.
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| Cell Assay |
For cellular assays, cells expressing a BMP-responsive luciferase reporter (BRE-Luc) are treated with BMP7 to stimulate signaling. Cells are pre-incubated with increasing concentrations of M4K2234 (0.1-1000 nM) for 1-2 hours, then BMP7 is added. After 16-24 hours, luciferase activity is measured to calculate the IC50 of 16 nM. SMAD1/5/8 phosphorylation is assessed by Western blot.
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| Animal Protocol |
No in vivo animal experiment data is available for M4K2234.
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| ADME/Pharmacokinetics |
A detailed pharmacokinetic profile for M4K2234 has not been reported in the provided references. As an orally active compound, it is designed to have favorable absorption properties.
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| Toxicity/Toxicokinetics |
No specific toxicology data is reported for M4K2234. As a highly selective chemical probe, it is designed to minimize off-target effects, potentially improving its safety profile.
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| References | |
| Additional Infomation |
M4K2234 (CAS: 2421141-51-5) is an orally active, highly selective inhibitor of ALK1 (IC50 = 7 nM) and ALK2 (IC50 = 14 nM). It specifically blocks BMP signaling by inhibiting SMAD1/5/8 phosphorylation and inhibits BMP7-stimulated reporter activity with an IC50 of 16 nM. It can be used for research in diffuse midline glioma (DMG) and fibrodysplasia ossificans progressiva (FOP). Molecular formula: C27H31FN4O2; molecular weight: 462.56.
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| Molecular Formula |
C27H31FN4O2
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|---|---|
| Molecular Weight |
462.559049844742
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| Exact Mass |
462.243
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| CAS # |
2421141-51-5
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| PubChem CID |
155548898
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| Appearance |
Light brown to brown solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
663
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(N)(=O)C1=C(OC)C=C(C2=C(C)C(C3=CC=C(N4CCN(C(C)C)CC4)C=C3)=CN=C2)C=C1F
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| InChi Key |
RIWTUJFFSTVYPW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H31FN4O2/c1-17(2)31-9-11-32(12-10-31)21-7-5-19(6-8-21)22-15-30-16-23(18(22)3)20-13-24(28)26(27(29)33)25(14-20)34-4/h5-8,13-17H,9-12H2,1-4H3,(H2,29,33)
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| Chemical Name |
2-fluoro-6-methoxy-4-[4-methyl-5-[4-(4-propan-2-ylpiperazin-1-yl)phenyl]pyridin-3-yl]benzamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (216.19 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1619 mL | 10.8094 mL | 21.6188 mL | |
| 5 mM | 0.4324 mL | 2.1619 mL | 4.3238 mL | |
| 10 mM | 0.2162 mL | 1.0809 mL | 2.1619 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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