Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDMVZD6)

• DOT Name: Porimin (TMEM123)
• Synonyms: Keratinocytes-associated transmembrane protein 3; KCT-3; Pro-oncosis receptor inducing membrane injury; Transmembrane protein 123
• Gene Name: TMEM123
• UniProt ID: PORIM_HUMAN
• Pfam ID: PF05283
• Sequence:
  MGLGARGAWAALLLGTLQVLALLGAAHESAAMAASANIENSGLPHNSSANSTETLQHVPS
  DHTNETSNSTVKPPTSVASDSSNTTVTTMKPTAASNTTTPGMVSTNMTSTTLKSTPKTTS
  VSQNTSQISTSTMTVTHNSSVTSAASSVTITTTMHSEAKKGSKFDTGSFVGGIVLTLGVL
  SILYIGCKMYYSRRGIRYRTIDEHDAII
• Function: Implicated in oncotic cell death, characterized by cell swelling, organelle swelling, vacuolization and increased membrane permeability.
• Tissue Specificity: Ubiquitous. Not expressed in ovary. Expressed in keratinocytes.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Porimin (TMEM123).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Porimin (TMEM123).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Porimin (TMEM123).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Porimin (TMEM123).	[4]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Porimin (TMEM123).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Porimin (TMEM123).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Porimin (TMEM123).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Porimin (TMEM123).	[8]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Porimin (TMEM123).	[9]

References

• [1] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [5] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [6] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [8] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [9] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.