Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGRPM9X)

• DOT Name: Protein lin-37 homolog (LIN37)
• Synonyms: Antolefinin
• Gene Name: LIN37
• UniProt ID: LIN37_HUMAN
• PDB ID: 7N40; 7R1D
• Pfam ID: PF15306
• Sequence:
  MFPVKVKVEKSELEMAKARNQLDAVLQCLLEKSHMDRERLDEEAGKTPSDTHNKDCSIAA
  TGKRPSARFPHQRRKKRREMDDGLAEGGPQRSNTYVIKLFDRSVDLAQFSENTPLYPICR
  AWMRNSPSVRERECSPSSPLPPLPEDEEGSEVTNSKSRDVYKLPPPTPPGPPGDACRSRI
  PSPLQPEMQGTPDDEPSEPEPSPSTLIYRNMQRWKRIRQRWKEASHRNQLRYSESMKILR
  EMYERQ
• KEGG Pathway: Cellular senescence (hsa04218)
• Reactome Pathway:
  Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 (R-HSA-1362300)
  G0 and Early G1 (R-HSA-1538133)
  Polo-like kinase mediated events (R-HSA-156711)
  Cyclin E associated events during G1/S transition (R-HSA-69202)
  G1/S-Specific Transcription (R-HSA-69205)
  Cyclin A (R-HSA-69656)
  Transcription of E2F targets under negative control by DREAM complex (R-HSA-1362277)

Molecular Interaction Atlas (MIA) of This DOT

4 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 Protein lin-37 homolog (LIN37).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Protein lin-37 homolog (LIN37).	[7]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Protein lin-37 homolog (LIN37).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Protein lin-37 homolog (LIN37).	[11]

7 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 Protein lin-37 homolog (LIN37).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein lin-37 homolog (LIN37).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein lin-37 homolog (LIN37).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein lin-37 homolog (LIN37).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein lin-37 homolog (LIN37).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein lin-37 homolog (LIN37).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein lin-37 homolog (LIN37).	[10]

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] 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.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] 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.
• [5] 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.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [9] Exposure to environmental bisphenol A inhibits HTR-8/SVneo cell migration and invasion. J Biomed Res. 2020 Jun 30;34(5):369-378. doi: 10.7555/JBR.34.20200013.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.