M4K-2009
Based on 1 Customer Validation
M4K-2009 is an orally bioactive ALK2 inhibitor with an IC50 of 13 nM. M4K-2009 exerts comparable inhibitory potency against wild-type and mutant ALK2G328V, ALK2R206H, and ALK2R258G. M4K-2009 exhibits moderate off-target inhibitory activity against hERG potassium channels. M4K-2009 can be used in studies related to diffuse intrinsic pontine glioma.
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté: 99.35%
- CAS No.: 2600795-07-9
- Formule: C25H29N3O3
- Masse moléculaire:419.52
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
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ALK2 |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | IC50 |
12 nM
Compound: 6a; M4K2009
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Competitive displacement of PBI-6908 from nanoluciferase-fused ALK2 R206H mutant (unknown origin) expressed in HEK293 cells incubated for 2 hrs by NanoBRET NanoGlo substrate based NanoBRET assay
Competitive displacement of PBI-6908 from nanoluciferase-fused ALK2 R206H mutant (unknown origin) expressed in HEK293 cells incubated for 2 hrs by NanoBRET NanoGlo substrate based NanoBRET assay
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[PMID: 32787083] |
| HEK293 | IC50 |
16 nM
Compound: 6a; M4K2009
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Competitive displacement of PBI-6908 from nanoluciferase-fused ALK2 G356D mutant (unknown origin) expressed in HEK293 cells incubated for 2 hrs by NanoBRET NanoGlo substrate based NanoBRET assay
Competitive displacement of PBI-6908 from nanoluciferase-fused ALK2 G356D mutant (unknown origin) expressed in HEK293 cells incubated for 2 hrs by NanoBRET NanoGlo substrate based NanoBRET assay
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[PMID: 32787083] |
| HEK293 | IC50 |
2712 nM
Compound: 6a; M4K2009
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Inhibition of recombinant human ALK5 expressed in HEK293 cells transfected with CAGA-luciferase and Renilla luciferase reporter after 24 hrs by dual luciferase reporter assay
Inhibition of recombinant human ALK5 expressed in HEK293 cells transfected with CAGA-luciferase and Renilla luciferase reporter after 24 hrs by dual luciferase reporter assay
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[PMID: 32787083] |
| HEK293 | IC50 |
45 nM
Compound: 6a; M4K2009
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Competitive displacement of PBI-6908 from nanoluciferase-fused ALK2 (unknown origin) expressed in HEK293 cells incubated for 2 hrs by NanoBRET NanoGlo substrate based NanoBRET assay
Competitive displacement of PBI-6908 from nanoluciferase-fused ALK2 (unknown origin) expressed in HEK293 cells incubated for 2 hrs by NanoBRET NanoGlo substrate based NanoBRET assay
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[PMID: 32787083] |
| HEK293 | IC50 |
6 nM
Compound: 6a; M4K2009
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Competitive displacement of PBI-6908 from nanoluciferase-fused ALK2 G328V mutant (unknown origin) expressed in HEK293 cells incubated for 2 hrs by NanoBRET NanoGlo substrate based NanoBRET assay
Competitive displacement of PBI-6908 from nanoluciferase-fused ALK2 G328V mutant (unknown origin) expressed in HEK293 cells incubated for 2 hrs by NanoBRET NanoGlo substrate based NanoBRET assay
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[PMID: 32787083] |
| HEK293 | IC50 |
7 nM
Compound: 6a; M4K2009
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Competitive displacement of PBI-6908 from nanoluciferase-fused ALK2 Q207D mutant (unknown origin) expressed in HEK293 cells incubated for 2 hrs by NanoBRET NanoGlo substrate based NanoBRET assay
Competitive displacement of PBI-6908 from nanoluciferase-fused ALK2 Q207D mutant (unknown origin) expressed in HEK293 cells incubated for 2 hrs by NanoBRET NanoGlo substrate based NanoBRET assay
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[PMID: 32787083] |
| HEK293 | IC50 |
8.3 μM
Compound: 6a; M4K2009
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Inhibition of human ERG expressed in HEK293 cells after 5 mins by IonWorks barracuda patch clamp method
Inhibition of human ERG expressed in HEK293 cells after 5 mins by IonWorks barracuda patch clamp method
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[PMID: 32787083] |
M4K-2009 (Compound 6a) potently inhibits wild-type recombinant ALK2 with an IC50 value of 13 nM, and maintains comparable inhibitory activity against ALK2G328V, ALK2R206H and ALK2R258G[1].
M4K-2009 inhibits wild-type ALK2 in HEK-293 cells with an IC50 of 45 nM, and exhibits potent activity against ALK2G328V, ALK2G356D, ALK2Q207D and ALK2R206H in the same cell line[1].
M4K-2009 (1 μM) exhibits high selectivity at the kinome-wide level. At a concentration of 1 μM, only 2.1% of the 374 tested kinases are inhibited by over 50%, and its potent off-target activity is restricted solely to DDR1 (IC50 = 41 nM) and TNIK (IC50 = 96 nM)[1].
M4K-2009 inhibits the viability of DIPG-XXI cells with a GI50 of 52 nM; it also inhibits the viability of HSJD-DIPG-007 cells with a GI50 of 130 nM[1].
M4K-2009 moderately inhibits
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD-SCID (male)[3]
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Dosage:25 mg/kg
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Administration:p.o.; single dose
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Result:Reached plasma concentration of 3021 nM at 0.5 h post-administration.
Reached plasma concentration of 4276 nM at 1 h post-administration.
Reached plasma concentration of 7489 nM at 2 h post-administration.
Reached plasma concentration of 13432 nM at 6 h post-administration.
Reached plasma concentration of 1542 nM at 24 h post-administration.
Chemical Information
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CAS No. 2600795-07-9
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Appearance Solid
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Masse moléculaire 419.52
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Formule C25H29N3O3
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Color White to light yellow
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SMILES
COC(C=C1C2=CN=CC(C3=CC=C(N4CCNCC4)C=C3)=C2C)=C(C(OC)=C1)OC
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
DMSO : 100 mg/mL (238.37 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.96 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.96 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureté et documentation
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Fiche technique (274 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instruction de manipulation (2659 KB)
Références
[1]. Smil D, et al. Leveraging an Open Science Drug Discovery Model to Develop CNS-Penetrant ALK2 Inhibitors for the Treatment of Diffuse Intrinsic Pontine Glioma. J Med Chem. 2020;63(17):10061-10085. [Content Brief]
[2]. Ensan D, et al. Targeting ALK2: An Open Science Approach to Developing Therapeutics for the Treatment of Diffuse Intrinsic Pontine Glioma. J Med Chem. 2020;63(9):4978-4996. [Content Brief]
[3]. González-Álvarez H, et al. Discovery of Conformationally Constrained ALK2 Inhibitors. J Med Chem. 2024;67(6):4707-4725. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3837 mL | 11.9184 mL | 23.8368 mL | 59.5919 mL |
| 5 mM | 0.4767 mL | 2.3837 mL | 4.7674 mL | 11.9184 mL | |
| 10 mM | 0.2384 mL | 1.1918 mL | 2.3837 mL | 5.9592 mL | |
| 15 mM | 0.1589 mL | 0.7946 mL | 1.5891 mL | 3.9728 mL | |
| 20 mM | 0.1192 mL | 0.5959 mL | 1.1918 mL | 2.9796 mL | |
| 25 mM | 0.0953 mL | 0.4767 mL | 0.9535 mL | 2.3837 mL | |
| 30 mM | 0.0795 mL | 0.3973 mL | 0.7946 mL | 1.9864 mL | |
| 40 mM | 0.0596 mL | 0.2980 mL | 0.5959 mL | 1.4898 mL | |
| 50 mM | 0.0477 mL | 0.2384 mL | 0.4767 mL | 1.1918 mL | |
| 60 mM | 0.0397 mL | 0.1986 mL | 0.3973 mL | 0.9932 mL | |
| 80 mM | 0.0298 mL | 0.1490 mL | 0.2980 mL | 0.7449 mL | |
| 100 mM | 0.0238 mL | 0.1192 mL | 0.2384 mL | 0.5959 mL |
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