Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYKE9ZM)

• DOT Name: Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1)
• Synonyms: Link guanine nucleotide exchange factor II; Link GEFII
• Gene Name: RAPGEFL1
• UniProt ID: RPGFL_HUMAN
• PDB ID: 2DHZ
• Pfam ID: PF00617
• Sequence:
  MKPLEKFLKKQTSQLAGRTVAGGPGGGLGSCGGPGGGGGPGGGGGPAGGQRSLQRRQSVS
  RLLLPAFLREPPAEPGLEPPVPEEGGEPAGVAEEPGSGGPCWLQLEEVPGPGPLGGGGPL
  RSPSSYSSDELSPGEPLTSPPWAPLGAPERPEHLLNRVLERLAGGATRDSAASDILLDDI
  VLTHSLFLPTEKFLQELHQYFVRAGGMEGPEGLGRKQACLAMLLHFLDTYQGLLQEEEGA
  GHIIKDLYLLIMKDESLYQGLREDTLRLHQLVETVELKIPEENQPPSKQVKPLFRHFRRI
  DSCLQTRVAFRGSDEIFCRVYMPDHSYVTIRSRLSASVQDILGSVTEKLQYSEEPAGRED
  SLILVAVSSSGEKVLLQPTEDCVFTALGINSHLFACTRDSYEALVPLPEEIQVSPGDTEI
  HRVEPEDVANHLTAFHWELFRCVHELEFVDYVFHGERGRRETANLELLLQRCSEVTHWVA
  TEVLLCEAPGKRAQLLKKFIKIAALCKQNQDLLSFYAVVMGLDNAAVSRLRLTWEKLPGK
  FKNLFRKFENLTDPCRNHKSYREVISKMKPPVIPFVPLILKDLTFLHEGSKTLVDGLVNI
  EKLHSVAEKVRTIRKYRSRPLCLDMEASPNHLQTKAYVRQFQVIDNQNLLFELSYKLEAN
  SQ
• Function: Probable guanine nucleotide exchange factor (GEF).

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[1]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[2]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[3]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[4]
Marinol	DM70IK5	Approved	Marinol increases the expression of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[5]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[6]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[6]
Estrone	DM5T6US	Approved	Estrone increases the expression of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[6]
Mestranol	DMG3F94	Approved	Mestranol increases the expression of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[11]
HEXESTROL	DM9AGWQ	Withdrawn from market	HEXESTROL increases the expression of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[6]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[13]

2 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 decreases the methylation of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Rap guanine nucleotide exchange factor-like 1 (RAPGEFL1).	[12]

References

• [1] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [2] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [3] 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.
• [4] DNA methylation inhibits p53-mediated survivin repression. Oncogene. 2009 May 14;28(19):2046-50. doi: 10.1038/onc.2009.62. Epub 2009 Apr 13.
• [5] 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.
• [6] Moving toward integrating gene expression profiling into high-throughput testing: a gene expression biomarker accurately predicts estrogen receptor alpha modulation in a microarray compendium. Toxicol Sci. 2016 May;151(1):88-103.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [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.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [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] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [13] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.