Art. -Nr.: HY-149591

M4K-2009

Name: M4K-2009
Brand: MedChemExpress
SKU: HY-149591
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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.

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Reinheit: 99.35%
CAS. Nr.: 2600795-07-9
Formel: C₂₅H₂₉N₃O₃
Molecular Weight:419.52

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

M4K-2009 Chemical Structure

CAS. Nr.: 2600795-07-9

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Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

IC₅₀ & Target

^[1]^[2]^[3]^[4]

ALK2

8-13 nM (IC₅₀)

potassium channel

8 μM (IC₅₀)

Alle TGF-β Receptor Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
HEK293	IC₅₀	12 nM Compound: 6a; M4K2009	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	[PMID: 32787083]
HEK293	IC₅₀	16 nM Compound: 6a; M4K2009	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	[PMID: 32787083]
HEK293	IC₅₀	2712 nM Compound: 6a; M4K2009	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	[PMID: 32787083]
HEK293	IC₅₀	45 nM Compound: 6a; M4K2009	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	[PMID: 32787083]
HEK293	IC₅₀	6 nM Compound: 6a; M4K2009	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	[PMID: 32787083]
HEK293	IC₅₀	7 nM Compound: 6a; M4K2009	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	[PMID: 32787083]
HEK293	IC₅₀	8.3 μM Compound: 6a; M4K2009	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	[PMID: 32787083]

In Vitro

M4K2009 (compound 6a) (1 μM) exhibits remarkable kinome-wide selectivity, with significant potency limited to DDR1, TNIK, and 6 other kinases at 1 μM^[1].
M4K2009 potently inhibits recombinant wild-type and mutant ALK2 with IC₅₀ values ranging from 8-13 nM, and shows high selectivity for ALK2 over ALK5 (187-fold), ALK3 (33-fold), and ALK4 (103-fold)^[1].
M4K2009 (2 h) inhibits wild-type and mutant ALK2 in HEK-293 cells with cellular IC₅₀ values ranging from 6-45 nM, and exhibits 60-fold cellular selectivity for ALK2 over ALK5^[1].
M4K2009 (3-10 μM) shows greater than 100-fold selectivity for ALK2 over cannabinoid CB₁ and adrenergic α₂A receptors, and has a manageable hERG potassium channel inhibition profile with an IC₅₀ of 8.3 μM^[1].
M4K2009 (30 μM) does not significantly inhibit major human CYP enzyme isoforms at concentrations up to 30 μM^[1].
M4K2009 (1 μM; 60 min) has moderate metabolic stability in mouse and human liver microsomes, high C_max-2 permeability with minimal efflux, and a druglike plasma protein binding profile^[1].
M4K2009 potently inhibits WT ALK2 with an IC₅₀ of 13 nM, shows equipotent activity against ALK2^G328V, ALK2^R206H, and ALK2^R258G mutants, and exhibits 141-fold selectivity for ALK2 over ALK5 in a radioactive in vitro biochemical kinase assay^[2].
M4K2009 moderately inhibits the hERG potassium channel in HEK293 cells with an IC₅₀ of 8 μM^[2].
M4K2009 potently inhibits purified ALK2 with an IC₅₀ of 13 nM and shows 187-fold selectivity over purified ALK5^[4].
M4K2009 inhibits ALK2 activity in HEK-293 cells with an IC₅₀ of 26 nM^[4].
M4K2009 inhibits ALK5 activity in HEK-293 cells with an IC₅₀ of 3297 nM and shows 126-fold cell-based selectivity for ALK2 over ALK5^[4].
M4K2009 shows moderate metabolic stability in mouse liver microsomes, with 65% remaining after 60 min at 37 °C^[4].
M4K2009 shows moderate metabolic stability in human liver microsomes, with 71% remaining after 60 min at 37 °C^[4].
M4K2009 has high Caco-2 monolayer permeability with a P_{app_AB} of 5.4 × 10^-6 cm/s and a low efflux ratio of 0.3^[4].
M4K2009 potently inhibits the growth of ACVR1-mutant patient-derived DIPG cell lines SU-DIPG-XXI (GI₅₀ = 52 nM) and HSJD-DIPG-007 (GI₅₀ = 130 nM) and downregulates ID1 expression^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Parmacokinetics

Species	Dose	Route	Bioavailability	CL	V_ss	T_1/2	C_max
Mice^[1]	2 mg/kg	i.v.	/	12.7 mL/min/kg	2.05 L/kg	3.11 h	6.16 μM
Mice^[1]	10 mg/kg	p.o.	100 %	/	/	/	/

In Vivo

M4K2009 (10-100 mg/kg; p.o.; single administration) exhibits excellent penetrability and can cross the blood-brain barrier in female CB17 SCID mice^[1].
M4K-2009 (25 mg/kg; p.o.; single administration) achieves high plasma exposure in healthy male NOD-SCID mice following a single oral dose of 25 mg/kg^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Female CB17 SCID mice^[1]
Dosage:

10 mg/kg; 100 mg/kg
Administration:

p.o.; single dose
Result:

Exhibited a dose-dependent increase in brain-to-plasma (B/P) ratios, which reached 0.90 at the dose of 10 mg/kg and 1.1 at 100 mg/kg.

Animal Model:

Male NOD-SCID mice^[4]
Dosage:

25 mg/kg
Administration:

p.o.; single dose
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

CAS. Nr. 2600795-07-9
Appearance Solid
Molecular Weight 419.52
Formel C₂₅H₂₉N₃O₃
Color White to light yellow
SMILES

COC(C=C1C2=CN=CC(C3=CC=C(N4CCNCC4)C=C3)=C2C)=C(C(OC)=C1)OC
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Lösungsmittel & Löslichkeit

In Vitro:

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.3837 mL

11.9184 mL

23.8368 mL

5 mM

0.4767 mL

2.3837 mL

4.7674 mL

10 mM

0.2384 mL

1.1918 mL

2.3837 mL

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.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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.

Protocol 1

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.

Protocol 2

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.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (5.96 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
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

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (278 KB)
SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[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. Journal of medicinal chemistry. 2020 Sep 10;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. Journal of medicinal chemistry. 2020 May 14;63(9):4978-4996. [Content Brief]

[3]. Murrell E, et al. Leveraging Open Science Drug Development for PET: Preliminary Neuroimaging of C-Labeled ALK2 Inhibitors. ACS medicinal chemistry letters. 2021 May 13;12(5):846-850. [Content Brief]

[4]. González-Álvarez H, et al. Discovery of Conformationally Constrained ALK2 Inhibitors. Journal of medicinal chemistry. 2024 Mar 28;67(6):4707-4725. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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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M4K-2009

Alle TGF-β Receptor Isoform-spezifische Produkte anzeigen