Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDEOB80)

• DOT Name: Allograft inflammatory factor 1-like (AIF1L)
• Synonyms: Ionized calcium-binding adapter molecule 2
• Gene Name: AIF1L
• Related Disease:
  Acute lymphocytic leukaemia
  Advanced cancer
  Childhood acute lymphoblastic leukemia
  Breast cancer
  Breast carcinoma
• UniProt ID: AIF1L_HUMAN
• PDB ID: 2JJZ; 2VTG
• Pfam ID: PF21008
• Sequence:
  MSGELSNRFQGGKAFGLLKARQERRLAEINREFLCDQKYSDEENLPEKLTAFKEKYMEFD
  LNNEGEIDLMSLKRMMEKLGVPKTHLEMKKMISEVTGGVSDTISYRDFVNMMLGKRSAVL
  KLVMMFEGKANESSPKPVGPPPERDIASLP
• Function: Actin-binding protein that promotes actin bundling. May neither bind calcium nor depend on calcium for function.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[2]

3 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 Allograft inflammatory factor 1-like (AIF1L).	[3]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Allograft inflammatory factor 1-like (AIF1L).	[15]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Allograft inflammatory factor 1-like (AIF1L).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Allograft inflammatory factor 1-like (AIF1L).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Allograft inflammatory factor 1-like (AIF1L).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Allograft inflammatory factor 1-like (AIF1L).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Allograft inflammatory factor 1-like (AIF1L).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Allograft inflammatory factor 1-like (AIF1L).	[8]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Allograft inflammatory factor 1-like (AIF1L).	[9]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Allograft inflammatory factor 1-like (AIF1L).	[10]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Allograft inflammatory factor 1-like (AIF1L).	[11]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of Allograft inflammatory factor 1-like (AIF1L).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Allograft inflammatory factor 1-like (AIF1L).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Allograft inflammatory factor 1-like (AIF1L).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Allograft inflammatory factor 1-like (AIF1L).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Allograft inflammatory factor 1-like (AIF1L).	[16]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Allograft inflammatory factor 1-like (AIF1L).	[17]

References

• [1] Two novel fusion genes, AIF1L-ETV6 and ABL1-AIF1L, result together with ETV6-ABL1 from a single chromosomal rearrangement in acute lymphoblastic leukemia with prenatal origin.Genes Chromosomes Cancer. 2018 Sep;57(9):471-477. doi: 10.1002/gcc.6. Epub 2018 Jul 30.
• [2] Absence of AIF1L contributes to cell migration and a poor prognosis of breast cancer.Onco Targets Ther. 2018 Sep 5;11:5485-5498. doi: 10.2147/OTT.S165874. eCollection 2018.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [10] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [11] Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin. J Neurochem. 2004 Mar;88(5):1211-9. doi: 10.1046/j.1471-4159.2003.02247.x.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [14] 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.
• [15] 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.
• [16] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [17] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.