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Chemical Structure| 866405-64-3 Chemical Structure| 866405-64-3

Structure of Dorsomorphin
CAS No.: 866405-64-3

Chemical Structure| 866405-64-3

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Dorsomorphin is a selective, ATP-competitive AMPK inhibitor (Ki of 109 nM in the absence of AMP) that selectively inhibits BMP type I receptors ALK2, ALK3, and ALK6, and reverses autophagy activation and anti-inflammatory effects induced by Urolithin A.

Synonyms: Compound C; BML-275

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Product Details of Dorsomorphin

CAS No. :866405-64-3
Formula : C24H25N5O
M.W : 399.49
SMILES Code : C(CN1CCCCC1)OC1=CC=C(C=C1)C1=CN2N=CC(=C2N=C1)C1=CC=NC=C1
Synonyms :
Compound C; BML-275
MDL No. :MFCD08705402
InChI Key :XHBVYDAKJHETMP-UHFFFAOYSA-N
Pubchem ID :11524144

Safety of Dorsomorphin

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H312-H332
Precautionary Statements:P280

Related Pathways of Dorsomorphin

epigenetics
PI3K-AKT

Isoform Comparison

Biological Activity

Target
  • AMPK

    AMPK, Ki:109 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
U937 cells 5 μM 24 h Enhanced cell death induced by navitoclax, S63845, or A-1155463. Cell Death Differ. 2024 Apr;31(4):405-416.
Hep3B cells 10 µM 16 h Dorsomorphin inhibited BMP2- and HJV-induced hepcidin promoter activity. Nat Chem Biol. 2008 Jan;4(1):33-41.
MRC-5 fetal lung fibroblasts 1 μM 4 days Dorsomorphin synergizes with FSK to promote neuronal survival and maturation, although independently DM has no effect on neuronal conversion. Nat Commun. 2013;4:2183.
IMR-90 fetal lung fibroblasts 1 μM 4 days Dorsomorphin synergizes with FSK to promote neuronal survival and maturation, although independently DM has no effect on neuronal conversion. Nat Commun. 2013;4:2183.
Clinical acute leukemia isolates 5 μM 24 h Synergized with navitoclax, venetoclax, A-1155463, or S63845 to enhance cell death. Cell Death Differ. 2024 Apr;31(4):405-416.
Jurkat cells 5 μM 24 h Inhibited navitoclax- or S63845-induced AMPKα autophosphorylation and substrate phosphorylation, enhancing cell death. Cell Death Differ. 2024 Apr;31(4):405-416.
C2C12 cells 4 µM 5 days Dorsomorphin inhibited 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 BMP-responsive SMADs, without affecting MAPK p38 activation. Nat Chem Biol. 2008 Jan;4(1):33-41.
Zebrafish embryos 0.312 μM or 0.625 μM To investigate the effects of DMP on zebrafish embryonic development, particularly on dorsoventral patterning. Results showed that DMP treatment caused dorsalization of embryos, similar to the phenotype induced by TDCIPP. Environ Sci Technol. 2018 Sep 18;52(18):10820-10828.
Saos2 cells 5 μM 24 h To investigate the effect of Dorsomorphin on the migration and invasion of Saos2 cells, results showed that Dorsomorphin significantly inhibited the migration and invasion induced by TMEM119 overexpression. Exp Mol Med. 2017 May 12;49(5):e329.
FOP fibroblasts 1 μM 25 days Inhibited BMP-SMAD signaling, significantly reducing iPSC generation from FOP fibroblasts Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):13057-13062.
WT-hepatocytes 10 µM 9 h Dorsomorphin completely restored the A23187-mediated inhibition of glycogen deposition, suggesting that the inhibitory effects of A23187 are mediated by AMPK signaling. Mol Metab. 2024 Jun;84:101942.
WT-hepatocytes 1, 3, or 10 µM 9 h Dorsomorphin reversed the ethanol-mediated inhibition of glycogen levels, indicating that ethanol suppresses glycogen deposition through the AMPK signaling pathway. Mol Metab. 2024 Jun;84:101942.
3T3-L1 fibroblasts 1 μmol/mL 24 h To verify whether AMPK mediates 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, U937, or MV-4-11 xenograft models Intraperitoneal injection 25 mg/kg Three times a week for two weeks The combination of dorsomorphin with navitoclax or S63845 significantly inhibited xenograft growth with minimal toxicity to normal tissues. Cell Death Differ. 2024 Apr;31(4):405-416.
Zebrafish Adult zebrafish Intraperitoneal injection 23 µg/g Single injection Dorsomorphin inhibited iron-induced hepatic SMAD1/5/8 phosphorylation and hepcidin expression. Nat Chem Biol. 2008 Jan;4(1):33-41.
Zebrafish Zebrafish embryos Exposure in embryo media 0.312 μM or 0.625 μM Exposure initiated at 0.75 hpf To investigate the effects of DMP on zebrafish embryonic development, particularly on dorsoventral patterning. Results showed that DMP treatment caused dorsalization of embryos, similar to the phenotype induced by TDCIPP. Environ Sci Technol. 2018 Sep 18;52(18):10820-10828.
Rats Streptozotocin-induced diabetic peripheral neuropathy model Intraperitoneal injection 0.2 mg/kg Once daily for 15 days To investigate the effect of Dorsomorphin on the protective role of Empagliflozin in diabetic peripheral neuropathy, 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

2.50mL

0.50mL

0.25mL

12.52mL

2.50mL

1.25mL

25.03mL

5.01mL

2.50mL

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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