Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSJOZ3O)

• DOT Name: FAD-dependent oxidoreductase domain-containing protein 2 (FOXRED2)
• Synonyms: Endoplasmic reticulum flavoprotein associated with degradation
• Gene Name: FOXRED2
• UniProt ID: FXRD2_HUMAN
• Pfam ID: PF13738
• Sequence:
  MGLSAAAPLWGPPGLLLAIALHPALSVPPRRDYCVLGAGPAGLQMAYFLQRAGRDYAVFE
  RAPRPGSFFTRYPRHRKLISINKRYTGKANAEFNLRHDWNSLLSHDPRLLFRHYSRAYFP
  DARDMVRYLGDFADTLGLRVQYNTTIAHVTLDKDRQAWNGHYFILTDQKGQVHQCSVLFV
  ATGLSVPNQVDFPGSEYAEGYESVSVDPEDFVGQNVLILGRGNSAFETAENILGVTNFIH
  MLSRSRVRLSWATHYVGDLRAINNGLLDTYQLKSLDGLLESDLTDLAILKDSKGKFHVTP
  KFFLEEANTNQSADSITLPQDDNDNFAMRVPYDRVIRCLGWNFDFSIFNKSLRLNSGNAF
  GKKYPLIRASYESKGSRGLFILGTASHSVDYRKSAGGFIHGFRYTVRAVHRLLEHRHHSV
  TWPATELPITQLTSSIVRRVNEASGLYQMFGVLADVILLKENSTAFEYLEEFPIQMLAQL
  ETLTGRKAKHGLFVINMEYGRNFSGPDKDVFFDDRSVGHTEDAWQSNFLHPVIYYYRYLP
  TEQEVRFRPAHWPLPRPTAIHHIVEDFLTDWTAPIGHILPLRRFLENCLDTDLRSFYAES
  CFLFALTRQKLPPFCQQGYLRMQGLVSTESLWQHRVESRLLRDYAPTGRRLEDSSQQLGD
  QEPLGSPLAPGPLAQSVDSNKEEL
• Function: Probable flavoprotein which may function in endoplasmic reticulum associated degradation (ERAD). May bind non-native proteins in the endoplasmic reticulum and target them to the ubiquitination machinery for subsequent degradation.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of FAD-dependent oxidoreductase domain-containing protein 2 (FOXRED2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of FAD-dependent oxidoreductase domain-containing protein 2 (FOXRED2).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of FAD-dependent oxidoreductase domain-containing protein 2 (FOXRED2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of FAD-dependent oxidoreductase domain-containing protein 2 (FOXRED2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of FAD-dependent oxidoreductase domain-containing protein 2 (FOXRED2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of FAD-dependent oxidoreductase domain-containing protein 2 (FOXRED2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of FAD-dependent oxidoreductase domain-containing protein 2 (FOXRED2).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of FAD-dependent oxidoreductase domain-containing protein 2 (FOXRED2).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of FAD-dependent oxidoreductase domain-containing protein 2 (FOXRED2).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of FAD-dependent oxidoreductase domain-containing protein 2 (FOXRED2).	[9]
Marinol	DM70IK5	Approved	Marinol increases the expression of FAD-dependent oxidoreductase domain-containing protein 2 (FOXRED2).	[10]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of FAD-dependent oxidoreductase domain-containing protein 2 (FOXRED2).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of FAD-dependent oxidoreductase domain-containing protein 2 (FOXRED2).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of FAD-dependent oxidoreductase domain-containing protein 2 (FOXRED2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of FAD-dependent oxidoreductase domain-containing protein 2 (FOXRED2).	[15]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [10] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [11] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [12] 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.
• [13] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [14] 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.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.