Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGIN5YK)

• DOT Name: Cell death regulator Aven (AVEN)
• Gene Name: AVEN
• Related Disease:
  Acute leukaemia
  Acute lymphocytic leukaemia
  Advanced cancer
  Childhood acute lymphoblastic leukemia
  Haematological malignancy
  Neoplasm
  T-cell acute lymphoblastic leukaemia
  Non-small-cell lung cancer
  Systemic sclerosis
  Adult glioblastoma
  Glioblastoma multiforme
  Mesothelioma
• UniProt ID: AVEN_HUMAN
• Sequence:
  MQAERGARGGRGRRPGRGRPGGDRHSERPGAAAAVARGGGGGGGGDGGGRRGRGRGRGFR
  GARGGRGGGGAPRGSRREPGGWGAGASAPVEDDSDAETYGEENDEQGNYSKRKIVSNWDR
  YQDIEKEVNNESGESQRGTDFSVLLSSAGDSFSQFRFAEEKEWDSEASCPKQNSAFYVDS
  ELLVRALQELPLCLRLNVAAELVQGTVPLEVPQVKPKRTDDGKGLGMQLKGPLGPGGRGP
  IFELKSVAAGCPVLLGKDNPSPGPSRDSQKPTSPLQSAGDHLEEELDLLLNLDAPIKEGD
  NILPDQTSQDLKSKEDGEVVQEEEVCAKPSVTEEKNMEPEQPSTSKNVTEEELEDWLDSM
  IS
• Function: Protects against apoptosis mediated by Apaf-1.
• Tissue Specificity: Highly expressed in testis, ovary, thymus, prostate, spleen, small intestine, colon, heart, skeletal muscle, liver, kidney and pancreas.
• Reactome Pathway:
  Regulation of the apoptosome activity (R-HSA-9627069)
  Formation of apoptosome (R-HSA-111458)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute leukaemia	DISDQFDI	Definitive	Altered Expression	[1]
Acute lymphocytic leukaemia	DISPX75S	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Definitive	Altered Expression	[1]
Haematological malignancy	DISCDP7W	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Definitive	Altered Expression	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[2]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[3]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[4]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[4]
Mesothelioma	DISKWK9M	Limited	Genetic Variation	[5]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Gefitinib	DM15F0X	Approved	Cell death regulator Aven (AVEN) affects the response to substance of Gefitinib.	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Cell death regulator Aven (AVEN).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Cell death regulator Aven (AVEN).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Cell death regulator Aven (AVEN).	[14]

10 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 Cell death regulator Aven (AVEN).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cell death regulator Aven (AVEN).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cell death regulator Aven (AVEN).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Cell death regulator Aven (AVEN).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Cell death regulator Aven (AVEN).	[11]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Cell death regulator Aven (AVEN).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Cell death regulator Aven (AVEN).	[10]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Cell death regulator Aven (AVEN).	[10]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Cell death regulator Aven (AVEN).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cell death regulator Aven (AVEN).	[16]

References

• [1] Overexpression of the anti-apoptotic protein AVEN contributes to increased malignancy in hematopoietic neoplasms.Oncogene. 2013 May 16;32(20):2586-91. doi: 10.1038/onc.2012.263. Epub 2012 Jul 2.
• [2] Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum Mol Genet. 2004 Dec 15;13(24):3029-43. doi: 10.1093/hmg/ddh331. Epub 2004 Oct 20.
• [3] A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.Hum Mol Genet. 2013 Oct 1;22(19):4021-9. doi: 10.1093/hmg/ddt248. Epub 2013 Jun 4.
• [4] miR-30e Blocks Autophagy and Acts Synergistically with Proanthocyanidin for Inhibition of AVEN and BIRC6 to Increase Apoptosis in Glioblastoma Stem Cells and Glioblastoma SNB19 Cells.PLoS One. 2016 Jul 7;11(7):e0158537. doi: 10.1371/journal.pone.0158537. eCollection 2016.
• [5] Transcriptome sequencing of malignant pleural mesothelioma tumors.Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3521-6. doi: 10.1073/pnas.0712399105. Epub 2008 Feb 26.
• [6] 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.
• [7] 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.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] 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.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [11] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [12] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [13] 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.
• [14] 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.
• [15] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [17] Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum Mol Genet. 2004 Dec 15;13(24):3029-43. doi: 10.1093/hmg/ddh331. Epub 2004 Oct 20.