Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6BK4EI)

• DOT Name: Mesenteric estrogen-dependent adipogenesis protein (MEDAG)
• Synonyms: Activated in W/Wv mouse stomach 3 homolog; hAWMS3; Mesenteric estrogen-dependent adipose 4; MEDA-4
• Gene Name: MEDAG
• UniProt ID: MEDAG_HUMAN
• Sequence:
  MAGAACEPVARPSLTSISSGELRSLWTCDCELALLPLAQLLRLQPGAFQLSGDQLVVARP
  GEPAAARGGFNVFGDGLVRLDGQLYRLSSYIKRYVELTNYCDYKDYRETILSKPMLFFIN
  VQTKKDTSKERTYAFLVNTRHPKIRRQIEQGMDMVISSVIGESYRLQFDFQEAVKNFFPP
  GNEVVNGENLSFAYEFKADALFDFFYWFGLSNSVVKVNGKVLNLSSTSPEKKETIKLFLE
  KMSEPLIRRSSFSDRKFSVTSRGSIDDVFNCNLSPRSSLTEPLLAELPFPSVLESEETPN
  QFI
• Function: Involved in processes that promote adipocyte differentiation, lipid accumulation, and glucose uptake in mature adipocytes.
• Tissue Specificity: Highly expressed in the visceral fat depot.

Molecular Interaction Atlas (MIA) of This DOT

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Mesenteric estrogen-dependent adipogenesis protein (MEDAG).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Mesenteric estrogen-dependent adipogenesis protein (MEDAG).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Mesenteric estrogen-dependent adipogenesis protein (MEDAG).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Mesenteric estrogen-dependent adipogenesis protein (MEDAG).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Mesenteric estrogen-dependent adipogenesis protein (MEDAG).	[5]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Mesenteric estrogen-dependent adipogenesis protein (MEDAG).	[6]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Mesenteric estrogen-dependent adipogenesis protein (MEDAG).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Mesenteric estrogen-dependent adipogenesis protein (MEDAG).	[8]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Mesenteric estrogen-dependent adipogenesis protein (MEDAG).	[9]

References

• [1] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [7] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.