M4K2009 hydrochloride
M4K2009 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.
For research use only. We do not sell to patients.
- CAS No.: 2772902-12-0
- Formula: C25H30ClN3O3
- Molecular Weight:455.98
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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ALK2 8-13 nM (IC50) |
potassium channel 8 μM (IC50) |
M4K2009 hydrochloride 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) hydrochloride 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 (compound 6a) (1 μM) hydrochloride exhibits remarkable kinome-wide selectivity, with significant potency limited to DDR1, TNIK, and 6 other kinases at 1 μM[1].
M4K2009 (3-10 μM) hydrochloride 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) hydrochloride does not significantly inhibit major human CYP enzyme isoforms at concentrations up to 30 μM[1].
M4K2009 (1 μM; 60 min) hydrochloride has moderate metabolic stability in mouse and human liver microsomes, high Cmax-2 permeability with minimal efflux, and a druglike plasma protein binding profile[1].
M4K2009 hydrochloride potently inhibits WT ALK2 with an IC50 of 13 nM, shows equipotent activity against ALK2G328V, ALK2R206H, and ALK2R258G mutants, and exhibits 141-fold selectivity for ALK2 over ALK5 in a radioactive in vitro biochemical kinase assay[2].
M4K2009 hydrochloride moderately inhibits the hERG potassium channel in HEK293 cells with an IC50 of 8 μM[2].
M4K2009 hydrochloride potently inhibits purified ALK2 with an IC50 of 13 nM and shows 187-fold selectivity over purified ALK5[4].
M4K2009 hydrochloride inhibits ALK2 activity in HEK-293 cells with an IC50 of 26 nM[4].
M4K2009 hydrochloride 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 hydrochloride shows moderate metabolic stability in mouse liver microsomes, with 65% remaining after 60 min at 37 °C[4].
M4K2009 hydrochloride shows moderate metabolic stability in human liver microsomes, with 71% remaining after 60 min at 37 °C[4].
M4K2009 hydrochloride has high Caco-2 monolayer permeability with a Papp_AB of 5.4 × 10-6 cm/s and a low efflux ratio of 0.3[4].
M4K2009 hydrochloride 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.
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.
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Animal Model:Female CB17 SCID mice[1]
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Dosage:10 mg/kg; 100 mg/kg
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Administration:p.o.; single dose
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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.
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Animal Model:Male NOD-SCID mice[4]
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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. 2772902-12-0
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Molecular Weight 455.98
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Formula C25H30ClN3O3
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SMILES
COC(C=C1C2=CN=CC(C3=CC=C(N4CCNCC4)C=C3)=C2C)=C(C(OC)=C1)OC.Cl
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[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]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
M4K2009 hydrochloride Related Classifications
HY-149591A Related Classifications
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