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.)

Preparing Stock Solutions

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.

+ Expand

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

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.