Dorsomorphin

Catalog No.S7840 Batch:S784002

Technical Data

Formula	C₂₄H₂₅N₅O
Molecular Weight	399.49	CAS No.	866405-64-3
Solubility (25°C)*	In vitro	Ethanol	5 mg/mL (12.51 mM)
		DMSO	2 mg/mL (5.0 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

Dorsomorphin is a potent, reversible, selective AMPK inhibitor with K_i of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6. Dorsomorphin is used in promoting specific cell differentiation and inducing cancer cell line autophagy. For animal testing, the water-soluble S7306 Dorsomorphin (Compound C) 2HCl is recommended.

Targets

ALK2 ^[3]	ALK3 ^[3]	ALK6 ^[3]	AMPK ^[1] (Cell-free assay)
			109 nM(Ki)

In vitro

Dorsomorphin inhibits ACC inactivation by either AICAR or metformin, and also attenuates AICAR and metformin’s effect to increase fatty acid oxidation or suppress lipogenic genes in hepatocytes. ^[1]

Inhibition of AMPK activity by Dorsomorphin almost completely inhibits autophagic proteolysis in HT-29 cells. ^[2]

In addition, Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6, and thus blocks BMP-mediated SMAD1/5/8 phosphorylation, target gene transcription and osteogenic differentiation. ^[3]

In vivo

Dorsomorphin (10 mg/kg) reduces basal levels of hepcidin expression and increases serum iron concentrations in adult mice. ^[3]

Dorsomorphin (0.2 mg/kg, i.v.) significantly reduces VCAM-1 and ICAM-1 expression in the thoracic aorta of LPS-treated rats. ^[4]

Protocol (from reference)

Kinase Assay:^{^[1]}	AMPK partial purification and in vitro kinase assay. Liver AMPK is partially purified from male SD rats to the blue-Sepharose step. The 100-μl reaction mixture contains 100 μM AMP, 100 μM ATP (0.5 μCi ³³P-ATP per reaction), and 50 μM SAMS in a buffer (40 mM HEPES, pH 7.0, 80 mM NaCl, 0.8 mM EDTA, 5 mM MgCl₂, 0.025% BSA, and 0.8 mM DTT). The reaction is initiated with addition of the enzyme. After 30-minute incubation at 30°C, the reaction is stopped by addition of 80 μl 1% H₃PO₄. Aliquots (100 μl) are transferred to 96-well MultiScreen plates. The plate is washed three times with 1% H3PO4 followed by detection in a Top-count. The in vitro AMPK inhibition data obtained with compound C — (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine — are fit to the following equation for competitive inhibition by nonlinear regression using a least-squares Marquardt algorithm in a computer program written by N. Thornberry of Merck Research Laboratories: Vi/Vo = (K_m + S)/[S + K_m × (1 + I/K_i)], where Vi is the inhibited velocity, Vo is the initial velocity, S is the substrate (ATP) concentration, K_m is the Michaelis constant for ATP, I is the inhibitor (compound C) concentration, and K_i is the dissociation constant for compound C.
Animal Study:^{^[3]}	Animal Models Iron-replete mice Dosages ~10 mg/kg Administration i.v.

Kinase Assay:^{^[1]}

AMPK partial purification and in vitro kinase assay.
Liver AMPK is partially purified from male SD rats to the blue-Sepharose step. The 100-μl reaction mixture contains 100 μM AMP, 100 μM ATP (0.5 μCi ³³P-ATP per reaction), and 50 μM SAMS in a buffer (40 mM HEPES, pH 7.0, 80 mM NaCl, 0.8 mM EDTA, 5 mM MgCl₂, 0.025% BSA, and 0.8 mM DTT). The reaction is initiated with addition of the enzyme. After 30-minute incubation at 30°C, the reaction is stopped by addition of 80 μl 1% H₃PO₄. Aliquots (100 μl) are transferred to 96-well MultiScreen plates. The plate is washed three times with 1% H3PO4 followed by detection in a Top-count. The in vitro AMPK inhibition data obtained with compound C — (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine — are fit to the following equation for competitive inhibition by nonlinear regression using a least-squares Marquardt algorithm in a computer program written by N. Thornberry of Merck Research Laboratories: Vi/Vo = (K_m + S)/[S + K_m × (1 + I/K_i)], where Vi is the inhibited velocity, Vo is the initial velocity, S is the substrate (ATP) concentration, K_m is the Michaelis constant for ATP, I is the inhibitor (compound C) concentration, and K_i is the dissociation constant for compound C.

Animal Study:^{^[3]}

Animal Models
Iron-replete mice
Dosages
~10 mg/kg
Administration
i.v.

References

[4] Kim YM, et al. Atherosclerosis. 2011, 219(1), 57-64.

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Customer Product Validation

: , , J Cell Physiol, 2017, 232(7):1893-1906

: , , Clin Exp Pharmacol Physiol, 2016, 43(1):125-34.

: Data from [Data independently produced by , , Oncotarget, 2016, 6(41):43605-19.]

: Data from [Data independently produced by , , Exp Cell Res, 2016, 345(1):25-36.]

Selleck's Dorsomorphin has been cited by 452 publications

Progranulin promotes regulatory T cells plasticity by mitochondrial metabolism through AMPK/PGC-1α pathway in ARDS [ Clin Immunol, 2024, 261:109940]	PubMed: 38365048
Ultrasound-targeted microbubble technology facilitates SAHH gene delivery to treat diabetic cardiomyopathy by activating AMPK pathway [ iScience, 2024, 27(2):108852]	PubMed: 38303706
Tiaogan daozhuo formula attenuates atherosclerosis via activating AMPK -PPARγ-LXRα pathway [ J Ethnopharmacol, 2024, 324:117814]	PubMed: 38286155
Cardioprotective effects of asiaticoside against diabetic cardiomyopathy: Activation of the AMPK/Nrf2 pathway [ J Cell Mol Med, 2024, 28(2):e18055]	PubMed: 38113341
Hypoglycemic effects of dracorhodin and dragon blood crude extract from Daemonorops draco [ Bot Stud, 2024, 65(1):8]	PubMed: 38446324
Metformin improves memory via AMPK/mTOR-dependent route in a rat model of Alzheimer's disease [ Iran J Basic Med Sci, 2024, 27(3):360-365.]	PubMed: 38333746
Transient naive reprogramming corrects hiPS cells functionally and epigenetically [ Nature, 2023, 620(7975):863-872]	PubMed: 37587336
Transient naive reprogramming corrects hiPS cells functionally and epigenetically [ Nature, 2023, 620(7975):863-872]	PubMed: 37587336
Dysregulated Lipid Synthesis by Oncogenic IDH1 Mutation Is a Targetable Synthetic Lethal Vulnerability [ Cancer Discov, 2023, 13(2):496-515]	PubMed: 36355448
ADP-dependent glucokinase controls metabolic fitness in prostate cancer progression [ Mil Med Res, 2023, 10(1):64]	PubMed: 38082365

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