Dorsomorphin, known as compound C, is a reversible selective ATP-competitive inhibitor of AMPK with Ki of 109 nM. Dorsomorphin can also inhibit the bone morphogenic protein (BMP) signaling and do not effect the expression of several structurally related kinases including ZAPK, SYK, PKCq, PKA, and JAK3[3]. In addition, dorsomorphin could stimulate the oxidation of long chain fatty acids independently in adipocytes by increasing carnitine palmitoyltransferase-1 (CPT1) activity[4] and remarkly reduce the adipogenic Differentiation of 3T3-L1 cells at 10 μM[5]. Compound C induces protective autophagy in cancer cells through AMPK inhibition-independent blockade of Akt/mTOR pathway[6]. In vivo, dorsomorphin induces dorsalization in zebrafish embryos and the differentiation of osteoblast[7].
Dorsomorphin 细胞实验
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.
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.
Dorsomorphin 动物实验
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.
Inhibition of BMPR1-mediated osteoblast differentiation in BMP4-stimulated mouse C2C12 cells assessed as decrease in alkaline phosphatase level at 4 uM by spectrophotometry
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