Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM7TWJZ)

• DOT Name: Erythroid differentiation-related factor 1 (EDRF1)
• Gene Name: EDRF1
• UniProt ID: EDRF1_HUMAN
• Sequence:
  MGDAKEAGAEGPPAGAAARGGLSLLSQGESEESSAQGSALFLGGNEVKSRAVVKYSSAPP
  RTAFARLEEKTDLKLPPANWLRESAKLGPAGTTILGNSKKSKPFSSFGMAYDFIDSVGND
  VDVVSDSENIKKLLKIPYSKSHVSMAVHRIGRTLLLDELDIQELFMRSSQTGDWTWLKEF
  YQRLIDQKWQRKKKSKEHWYQKAILSKFLYYSINGDGAAQPVSSTAEQQESSSSDQTNDS
  EGASWPAPFEMPSSVSEDPSASSQGSEPLEPSYIVGHVASAPKEQNLITLFNDGEHSQGL
  KNDFVRNILWTFEDIHMLVGSNMPIFGGGRYPAVSLRLRDNNKPINVLTGIDYWLDNLIC
  NVPELVMCFHVNGIVQKYEMIKTEEIPNLENSNFSTKVIKDIAQNILSFLKSNCTKEGHT
  YWLFKASGSDIVKLYDLTTLCEETEDKYQNPFTMPVAILLYKVACNMMMKKNQNKKHYGT
  IRTLLLNCLKLLDKSRHPQIIASANYMLSELFQLDEPKKEENSESPLNENSDESYSEEEE
  EMPDSDENGSYSTSSDPSDDSKAVAIIKSVGELSVPEKYKSIHQIRPSCAFPVCHDTEER
  CRLVLSYVLEGLKSVDSSIKKESDLPAADPSTPIPLKYEDESSRGGPEGLEKQMALFLDK
  MGSLQKGNYSSQSGMIPGSWQHKMKLQLILKSSKAYYVLSDAAMSLQKYGRALRYIKLAL
  QSHDTYCCLCTNMLSEVLLFLSQYLTLCGDIQLMLAQNANNRAAHLEEFHYQTKEDQEIL
  HSLHRESSCQGFAWATDLSTDLESQLSVSCKCYEAANEILQFSDLKSQNPEHYVQVLKRM
  GNIRNEIGVFYMNQAAALQSERLVSKSVSAAEQQLWKKSFSCFEKGIHNFESIEDATNAA
  LLLCNTGRLMRICAQAHCGAGDELKREFSPEEGLYYNKAIDYYLKALRSLGTRDIHPAVW
  DSVNWELSTTYFTMATLQQDYAPLSRKAQEQIEKEVSEAMMKSLKYCDVDSVSARQPLCQ
  YRAATIHHRLASMYHSCLRNQVGDEHLRKQHRVLADLHYSKAAKLFQLLKDAPCELLRVQ
  LERVAFAEFQMTSQNSNVGKLKTLSGALDIMVRTEHAFQLIQKELIEEFGQPKSGDAAAA
  ADASPSLNREEVMKLLSIFESRLSFLLLQSIKLLSSTKKKTSNNIEDDTILKTNKHIYSQ
  LLRATANKTATLLERINVIVHLLGQLAAGSAASSNAVQ
• Function: Transcription factor involved in erythroid differentiation. Involved in transcriptional activation of the globin gene.

Molecular Interaction Atlas (MIA) of This DOT

11 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 Erythroid differentiation-related factor 1 (EDRF1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Erythroid differentiation-related factor 1 (EDRF1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Erythroid differentiation-related factor 1 (EDRF1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Erythroid differentiation-related factor 1 (EDRF1).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Erythroid differentiation-related factor 1 (EDRF1).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Erythroid differentiation-related factor 1 (EDRF1).	[6]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Erythroid differentiation-related factor 1 (EDRF1).	[7]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Erythroid differentiation-related factor 1 (EDRF1).	[2]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Erythroid differentiation-related factor 1 (EDRF1).	[9]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Erythroid differentiation-related factor 1 (EDRF1).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Erythroid differentiation-related factor 1 (EDRF1).	[11]

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 Erythroid differentiation-related factor 1 (EDRF1).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
• [7] Resveratrol inhibits pancreatic cancer cell proliferation through transcriptional induction of macrophage inhibitory cytokine-1. J Surg Res. 2007 Apr;138(2):163-9. doi: 10.1016/j.jss.2006.05.037. Epub 2007 Jan 25.
• [8] 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.
• [9] 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.
• [10] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [11] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.