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Chemical Structure| 1219168-18-9 Chemical Structure| 1219168-18-9

Structure of Dorsomorphin 2HCl
CAS No.: 1219168-18-9

Chemical Structure| 1219168-18-9

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Dorsomorphin 2HCl is an AMPK inhibitor with an IC50 value of 109 nM for AMPK. Dorsomorphin 2HCl inhibits the BMP signaling pathway and can be used in research on stem cell differentiation and bone regeneration.

Synonyms: Compound C dihydrochloride; BML-275 dihydrochloride; CpdC

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Product Citations

Product Citations

Hu, Chunli ; Dou, Wenli ; Ma, Xuehu ; An, Yanhao ; Wang, Dezhi ; Ma, Yanfen

Abstract: Mastitis, a serious threat to the health and milk production function of dairy cows decreasesmilk quality. Blood from three healthy cows and three mastitis cows were collected in thisstudy and their transcriptome was sequenced using the Illumina HiSeq platform. Differentiallyexpressed genes (DEGs) were screened according to the |log2FoldChange| > 1 and P-value <0.05 criteria. Pathway enrichment and functional annotation were performed through KEGGand GO analyses. Finally, the mechanism of the AMP-activated protein kinase (AMPK)mediation of (-)-epigallocatechin-3-gallate (EGCG) to promote lipid metabolism in mastitiscows was analyzed in bovine mammary epithelial cells (BMECs). Transcriptome analysisrevealed a total of 825 DEGs, with 474 genes showing increased expression and 351 genesshowing decreased expression. The KEGG analysis of DEGs revealed that they were mainlylinked to tumour necrosis factor, nuclear factor-κB signalling pathway, and lipidmetabolism-related signalling pathway, whereas GO functional annotation found that DEGswere enriched in threonine and methionine kinase activity, cellular metabolic processes, andcytoplasm. AMPK expression, which is involved in several lipid metabolism pathways, wasdownregulated in mastitis cows. The results of in vitro experiments showed that the inhibitionof AMPK promoted the expression of lipid synthesis genes in lipopolysaccharide-inducedBMECs and that EGCG could promote lipid synthesis by decreasing the expression of AMPKand downregulating the expression of inflammatory factors in inflammatory BMECs. Inconclusion, our study demonstrated that AMPK mediated EGCG to inhabit of inflammatoryresponses and promote of lipid synthesis in inflammatory BMECs.

Keywords: transcriptome ; AmPK ; egcg ; mastitis ; cow

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Product Details of Dorsomorphin 2HCl

CAS No. :1219168-18-9
Formula : C24H27Cl2N5O
M.W : 472.41
SMILES Code : [H]Cl.[H]Cl.C12=C(C3=CC=NC=C3)C=NN1C=C(C4=CC=C(OCCN5CCCCC5)C=C4)C=N2
Synonyms :
Compound C dihydrochloride; BML-275 dihydrochloride; CpdC
MDL No. :MFCD11112197
InChI Key :RJDVIJJQKMGPMV-UHFFFAOYSA-N
Pubchem ID :49761481

Safety of Dorsomorphin 2HCl

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Hep3B cells 10 µM 16 h Dorsomorphin abrogated BMP2- and HJV-induced hepcidin promoter activity. Nat Chem Biol. 2008 Jan;4(1):33-41.
Human fetal lung fibroblasts (IMR-90 or MRC-5) 1 μM 4 days Promotes neuronal survival and maturation, synergizes with FSK to significantly enhance neuronal conversion efficiency Nat Commun. 2013;4:2183.
Clinical acute leukemia isolates 5 μM 24 h Enhanced cell death induced by navitoclax or S63845 Cell Death Differ. 2024 Apr;31(4):405-416.
U937 cells 5 μM 24 h Inhibited AMPK activation and enhanced cell death induced by navitoclax or S63845 Cell Death Differ. 2024 Apr;31(4):405-416.
Jurkat cells 5 μM 24 h Inhibited AMPK activation and enhanced cell death induced by navitoclax or S63845 Cell Death Differ. 2024 Apr;31(4):405-416.
HepG2 cells 10 µM Dorsomorphin significantly reduced basal hepcidin expression in HepG2 cells and completely abolished BMP2-induced hepcidin expression. Nat Chem Biol. 2008 Jan;4(1):33-41.
C2C12 cells 4 µM 5 days Dorsomorphin almost completely abolished BMP4- and BMP6-induced alkaline phosphatase activity, indicating inhibition of BMP-induced osteogenic differentiation. Nat Chem Biol. 2008 Jan;4(1):33-41.
mouse pulmonary artery smooth muscle cells (PASMCs) 0.47 µM 30 min Dorsomorphin inhibited BMP4-induced phosphorylation of SMAD1/5/8, but did not affect MAPK p38 activation. Nat Chem Biol. 2008 Jan;4(1):33-41.
zebrafish embryos 0.312 μM or 0.625 μM 0.75 hpf to 24 hpf To investigate the effects of Dorsomorphin on early zebrafish embryogenesis, results showed that Dorsomorphin-treated embryos exhibited dorsalization phenotypes by 24 hpf. Environ Sci Technol. 2018 Sep 18;52(18):10820-10828.
Saos2 cells 5 μM Dorsomorphin inhibited the promoting effects of TMEM119 overexpression on Saos2 cell migration and invasion Exp Mol Med. 2017 May 12;49(5):e329.
FOP HDFs 1 μM 25 days Inhibits BMP-SMAD signaling, significantly reduces hiPSC generation from FOP HDFs Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):13057-13062.
WT-hepatocytes 10 µM 9 h To investigate the reversal effect of Dorsomorphin on A23187-mediated glycogen deposition suppression, results showed that Dorsomorphin completely restored the A23187-mediated reduction in glycogen content. Mol Metab. 2024 Jun;84:101942.
WT-hepatocytes 1, 3, or 10 µM 9 h To investigate the reversal effect of Dorsomorphin on ethanol-mediated glycogen depletion, results showed that Dorsomorphin reversed the ethanol-mediated inhibition of glycogen levels in a dose-dependent manner. Mol Metab. 2024 Jun;84:101942.
3T3-L1 fibroblasts 1 μmol/mL 24 h To verify whether AMPK mediated the anti-fibrotic effect of ORM, results showed that dorsomorphin reversed the inhibitory effect of ORM on fibrotic markers. Acta Pharmacol Sin. 2022 Feb;43(2):367-375.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
BALB/c Nude mice Jurkat xenograft model Intraperitoneal injection 25 mg/kg Three times a week for two weeks Inhibited xenograft tumor growth without increasing toxicity in normal tissues Cell Death Differ. 2024 Apr;31(4):405-416.
Zebrafish Zebrafish embryos Added to culture medium 10 µM Starting 4 h post fertilization (h.p.f.) and assessed visually at 24 and 48 h.p.f. Dorsomorphin treatment caused dorsalization of zebrafish embryos, manifested as expansion of dorsal structures and loss of ventral structures. Nat Chem Biol. 2008 Jan;4(1):33-41.
Rats Streptozotocin-induced diabetic peripheral neuropathy model Intraperitoneal injection 0.2 mg/kg Once daily for 15 days Dorsomorphin, as an AMPK inhibitor, was used to investigate the mechanism of Empagliflozin in diabetic peripheral neuropathy. The results showed that dorsomorphin almost completely abolished the beneficial effects of Empagliflozin. Arch Pharm Res. 2022 Jul;45(7):475-493

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.12mL

0.42mL

0.21mL

10.58mL

2.12mL

1.06mL

21.17mL

4.23mL

2.12mL

Dissolving Methods
The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1

References

 

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