Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2URF18)

• DOT Name: Interferon-related developmental regulator 2 (IFRD2)
• Synonyms: Protein SKMC15
• Gene Name: IFRD2
• Related Disease:
  Colitis
  Neoplasm
• UniProt ID: IFRD2_HUMAN
• Pfam ID: PF05004 ; PF04836
• Sequence:
  MPRARKGNTLRKGGQRRGGGARSSAQADSGSSDDEAASEARSTASECPSLLSTTAEDSLG
  GDVVDEQGQQEDLEEKLKEYVDCLTDKSAKTRQGALESLRLALASRLLPDFLLERRLTLA
  DALEKCLKKGKGEEQALAAAVLGLLCVQLGPGPKGEELFHSLQPLLVSVLSDSTASPAAR
  LHCASALGLGCYVAAADIQDLVSCLACLESVFSRFYGLGGSSTSPVVPASLHGLLSAALQ
  AWALLLTICPSTQISHILDRQLPRLPQLLSSESVNLRIAAGETIALLFELARDLEEEFVY
  EDMEALCSVLRTLATDSNKYRAKADRRRQRSTFRAVLHSVEGGECEEEIVRFGFEVLYMD
  SWARHRIYAAFKEVLGSGMHHHLQNNELLRDIFGLGPVLLLDATALKACKVPRFEKHLYN
  AAAFKARTKARSRVRDKRADIL
• Function: Ribosome-binding protein that acts as an inhibitor of mRNA translation by promoting ribosome inactivation. Associates with the P- and E-sites of the ribosome and inserts a C-terminal helix into the mRNA exit channel to preclude translation.
• Tissue Specificity: Expressed in many tissues including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colitis	DISAF7DD	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Interferon-related developmental regulator 2 (IFRD2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Interferon-related developmental regulator 2 (IFRD2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Interferon-related developmental regulator 2 (IFRD2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interferon-related developmental regulator 2 (IFRD2).	[6]
Selenium	DM25CGV	Approved	Selenium increases the expression of Interferon-related developmental regulator 2 (IFRD2).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Interferon-related developmental regulator 2 (IFRD2).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Interferon-related developmental regulator 2 (IFRD2).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interferon-related developmental regulator 2 (IFRD2).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Interferon-related developmental regulator 2 (IFRD2).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Interferon-related developmental regulator 2 (IFRD2).	[12]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Interferon-related developmental regulator 2 (IFRD2).	[13]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Interferon-related developmental regulator 2 (IFRD2).	[14]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Interferon-related developmental regulator 2 (IFRD2).	[15]

References

• [1] Identification of New Potential Therapies for Colitis Amelioration Using an Appendicitis-Appendectomy Model.Inflamm Bowel Dis. 2019 Feb 21;25(3):436-444. doi: 10.1093/ibd/izy332.
• [2] Small molecules targeted to the microtubule-Hec1 interaction inhibit cancer cell growth through microtubule stabilization.Oncogene. 2018 Jan 11;37(2):231-240. doi: 10.1038/onc.2017.320. Epub 2017 Sep 18.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [8] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [11] 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.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [14] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [15] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.