Dorsomorphin is an effective and specific inhibitor of AMPK (AMP-activated protein kinase), which is induced by AICAR and metformin.

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]

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]

HT1080 cells are seeded in 24-well plates (2×104 cells per well) and treated with Dorsomorphin in the presence or absence of glucose or 10 mM 2DG for 2 h. HT1080 cells that overexpressed the wild-type and dominant negative AMPKα1 are prepared by transfecting plasmid DNA (pAMPKα1-wt, pAMPKα1-D168A and pcFlag as a control) in 6-well plates, seeding in 24-well plate and treating with UPR inhibitors. Cells are lysed with cell lysis buffer (20 mM Tris-HCl, pH 7.5, 250 mM NaCl, 10% glycerol, 0.5% NP-40, 1 mM EDTA, 1 mM EGTA, 0.2 mM PMSF, 1 μg/mL pepstatin, 0.5 μg/mL leupeptin, 5 mM NaF, 2 mM Na3Vo4, 2 mM β-glycerophosphate, 1 mM DTT). Relative AMPK kinase activity (mean±SD of duplicate determinations) to control sample (vehicle or pcFlag under normal growth conditions) is determined using the CycLex AMPK kinase assay kit[2].

Dorsomorphin is dissolved in DMSO (10 mM) and stored,and then diluted with appropriate media (DMSO 0.5%) before use[2].HeLa and 786-O cells are treated with various concentrations of Dorsomorphin (0,0.3,1,3,10 μM ),Versipelostatin and Phenformin in the presence or absence of 10 mM 2DG or 1 μg/mL of Tunicamycin as a stressor for 30 h in 96-well plates.For the combination study,786-O cells are treated with various concentrations of UPR inhibitors in the presence or absence of 10 mM 2DG for 24 h.The medium is then replaced with fresh growth medium,and cells are cultured for a further 15 h.Subsequently,MTT is added to the culture medium,and the absorbance of each well is determined.For the viability assay under glucose-withdrawal conditions,HT1080 cells are treated with various concentrations of Dorsomorphin and phenformin in 12-well plates in the presence or absence of glucose for 18 h,seeded in 96-well plates with growth medium,and then cultured for a further 48 h before MTT is added.Relative cell survival (mean±SD of quadruplicate determinations) is calculated by setting each control absorbance from untreated cells as 100%.The effects of drug combinations at concentrations producing 80% cell growth inhibition (IC80) are analyzed using the isobologram method[2].

866405-64-3

C24H25N5O

399.49

Compound C;BML-275;Dorsomorphin

[1]Yu PB, et al. Nat Chem Biol. 2008, 4(1), 33-41. [2]He Y, Xu K, Wang Y, et al. AMPK as a potential pharmacological target for alleviating LPS-induced acute lung injury partly via NLRC4 inflammasome pathway inhibition[J]. Experimental Gerontology. 2019: 110661. [3]Kim YM, et al. Atherosclerosis. 2011, 219(1), 57-64. [4]Ma L, Gong F, Xu J, et al. Uncarboxylated osteocalcin reverses the high glucose?induced inhibition of the osteogenic differentiation of MC3T3E1 cells via the GPRC6A/cAMP/PKA/AMPK signaling pathway[J]. International Journal of Molecular Medicine. 2021, 47(5): 1-11 [5]Wu Y, Zeng S, Wan B, et al. Sophoricoside attenuates lipopolysaccharide-induced acute lung injury by activating the AMPK/Nrf2 signaling axis[J]. International Immunopharmacology. 2020: 107187. [6]Meley D, et al. J Biol Chem. 2006, 281(46), 34870-34879. [7]Wu Y, Zeng S, Wan B, et al. Sophoricoside attenuates lipopolysaccharide-induced acute lung injury by activating the AMPK/Nrf2 signaling axis[J]. International Immunopharmacology. 2021, 90: 107187 [8]Zhou G, et al. J Clin Invest. 2001, 108(8), 1167-1174. [9]Wang X D, Yu W L, Sun Y. Activation of AMPK restored impaired autophagy and inhibited inflammation reaction by up-regulating SIRT1 in acute pancreatitis[J]. Life Sciences. 2021: 119435. [10]Yang, Feihong, et al. Vaspin alleviates myocardial ischaemia/reperfusion injury via activating autophagic flux and restoring lysosomal function [J]. Biochemical and biophysical research communications. 2018 Sep 5;503(2):501-507.

[1]Wu A G, Pan R, Law B Y K, et al.  Targeting autophagy as a therapeutic strategy for identification of liganans from Peristrophe japonica in Parkinson’s disease. Signal transduction and targeted therapy. 2021, 6(1): 1-3. [2]Cao B, Zhang Y, Chen J, et al. Neuroprotective effects of liraglutide against inflammation through the AMPK/NF-κB pathway in a mouse model of Parkinson’s disease. Metabolic Brain Disease. 2021: 1-12. [3]Cao B, Zhang Y, Chen J, et al. Neuroprotective effects of liraglutide against inflammation through the AMPK/NF-κB pathway in a mouse model of Parkinson's disease. Metabolic Brain Disease. 2022, 37(2): 451-462 [4]Yang F, Xue L, Han Z, et al. Vaspin alleviates myocardial ischaemia/reperfusion injury via activating autophagic flux and restoring lysosomal function. Biochemical and Biophysical Research Communications. 2018, 503(2): 501-507 [5]He Y, Xu K, Wang Y, et al. AMPK as a potential pharmacological target for alleviating LPS-induced acute lung injury partly via NLRC4 inflammasome pathway inhibition. Experimental Gerontology. 2019: 110661. [6]Ma L, Gong F, Xu J, et al. Uncarboxylated osteocalcin reverses the high glucose?induced inhibition of the osteogenic differentiation of MC3T3E1 cells via the GPRC6A/cAMP/PKA/AMPK signaling pathway. International Journal of Molecular Medicine. 2021 May;47(5):91. doi: 10.3892/ijmm.2021.4924. Epub 2021 Mar 31. [7]Bai G, Chen B, Xiao X, et al. Geniposide inhibits cell proliferation and migration in human oral squamous carcinoma cells via AMPK and JNK signaling pathways. Experimental and Therapeutic Medicine. 2022, 24(6): 1-10. [8]Gao, Le, et al. Uncarboxylated osteocalcin promotes osteogenesis and inhibits adipogenesis of mouse bone marrow?derived mesenchymal stem cells via the PKA?AMPK?SIRT1 axis. Experimental and Therapeutic Medicine. 22.2 (2021): 1-13. [9]Rao X S, Cong X X, Gao X K, et al. AMPK-mediated phosphorylation enhances the auto-inhibition of TBC1D17 to promote Rab5-dependent glucose uptake. Cell Death & Differentiation. 2021: 1-21. [10]Jiang M, Xiao Y, Weigao E, et al. Characterization of the Zebrafish Cell Landscape at Single-Cell Resolution. Frontiers in Cell and Developmental Biology. 2021, 9.

DMSO:10mM,Need ultrasonic and warming and heat to 80°C
Powder: -20°C for 3 years
In solvent: -80°C for 2 years