Dorsomorphin

Catalog No.S7840 Batch:S784004

Technical Data

Formula	C₂₄H₂₅N₅O
Molecular Weight	399.49	CAS No.	866405-64-3
Solubility (25°C)*	In vitro	DMSO	5 mg/mL warmed with 50ºC water bath (12.51 mM)
		Water	Insoluble
		Ethanol	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 cell 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, and also attenuates AICAR’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 472 publications

ALKBH5 governs human endoderm fate by regulating the DKK1/4-mediated Wnt/β-catenin activation [ Nucleic Acids Res, 2024, gkae707]	PubMed: 39166492
Autism patient-derived SHANK2BY29X mutation affects the development of ALDH1A1 negative dopamine neuron [ Mol Psychiatry, 2024, 10.1038/s41380-024-02578-6]	PubMed: 38704506
Progranulin promotes regulatory T cells plasticity by mitochondrial metabolism through AMPK/PGC-1α pathway in ARDS [ Clin Immunol, 2024, 261:109940]	PubMed: 38365048
A splice site variant in MADD affects hormone expression in pancreatic β cells and pituitary gonadotropes [ JCI Insight, 2024, 9(10)e167598]	PubMed: 38775154
Metformin enhances endogenous neural stem cells proliferation, neuronal differentiation, and inhibits ferroptosis through activating AMPK pathway after spinal cord injury [ J Transl Med, 2024, 22(1):723]	PubMed: 39103875
Artemisinin conferred cytoprotection to human retinal pigment epithelial cells exposed to amiodarone-induced oxidative insult by activating the CaMKK2/AMPK/Nrf2 pathway [ J Transl Med, 2024, 22(1):844]	PubMed: 39285426
Methionine deficiency inhibited pyroptosis in primary hepatocytes of grass carp (Ctenopharyngodon idella): possibly via activating the ROS-AMPK-autophagy axis [ J Anim Sci Biotechnol, 2024, 15(1):116]	PubMed: 39218924
Multiple factors to assist human-derived induced pluripotent stem cells to efficiently differentiate into midbrain dopaminergic neurons [ Neural Regen Res, 2024, 19(4):908-914]	PubMed: 37843228
Calpain-1 Up-Regulation Promotes Bleomycin-Induced Pulmonary Fibrosis by Activating Ferroptosis [ Am J Pathol, 2024, S0002-9440(24)00356-0]	PubMed: 39326733
Ultrasound-targeted microbubble technology facilitates SAHH gene delivery to treat diabetic cardiomyopathy by activating AMPK pathway [ iScience, 2024, 27(2):108852]	PubMed: 38303706

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