Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT87E7HW)

• DOT Name: Apoptosis facilitator Bcl-2-like protein 14 (BCL2L14)
• Synonyms: Bcl2-L-14; Apoptosis regulator Bcl-G
• Gene Name: BCL2L14
• Related Disease:
  Breast neoplasm
  Prostate cancer
  Prostate carcinoma
  Triple negative breast cancer
• UniProt ID: B2L14_HUMAN
• Sequence:
  MCSTSGCDLEEIPLDDDDLNTIEFKILAYYTRHHVFKSTPALFSPKLLRTRSLSQRGLGN
  CSANESWTEVSWPCRNSQSSEKAINLGKKKSSWKAFFGVVEKEDSQSTPAKVSAQGQRTL
  EYQDSHSQQWSRCLSNVEQCLEHEAVDPKVISIANRVAEIVYSWPPPQATQAGGFKSKEI
  FVTEGLSFQLQGHVPVASSSKKDEEEQILAKIVELLKYSGDQLERKLKKDKALMGHFQDG
  LSYSVFKTITDQVLMGVDPRGESEVKAQGFKAALVIDVTAKLTAIDNHPMNRVLGFGTKY
  LKENFSPWIQQHGGWEKILGISHEEVD
• Function: Plays a role in apoptosis.
• Tissue Specificity: Isoform 1 is widely expressed. Isoform 2 is testis-specific.
• Reactome Pathway: TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain (R-HSA-6803205)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[1]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]
Triple negative breast cancer	DISAMG6N	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Apoptosis facilitator Bcl-2-like protein 14 (BCL2L14).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Apoptosis facilitator Bcl-2-like protein 14 (BCL2L14).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Apoptosis facilitator Bcl-2-like protein 14 (BCL2L14).	[6]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Apoptosis facilitator Bcl-2-like protein 14 (BCL2L14).	[7]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Apoptosis facilitator Bcl-2-like protein 14 (BCL2L14).	[8]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate increases the expression of Apoptosis facilitator Bcl-2-like protein 14 (BCL2L14).	[9]
Sanguinarine	DMDINFS	Approved	Sanguinarine increases the expression of Apoptosis facilitator Bcl-2-like protein 14 (BCL2L14).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Apoptosis facilitator Bcl-2-like protein 14 (BCL2L14).	[11]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Apoptosis facilitator Bcl-2-like protein 14 (BCL2L14).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Apoptosis facilitator Bcl-2-like protein 14 (BCL2L14).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Apoptosis facilitator Bcl-2-like protein 14 (BCL2L14).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Apoptosis facilitator Bcl-2-like protein 14 (BCL2L14).	[14]

References

• [1] Medullary Breast Carcinoma, a Triple-Negative Breast Cancer Associated with BCLG Overexpression.Am J Pathol. 2018 Oct;188(10):2378-2391. doi: 10.1016/j.ajpath.2018.06.021. Epub 2018 Aug 1.
• [2] Expression mapping at 12p12-13 in advanced prostate carcinoma.Int J Cancer. 2004 May 1;109(5):668-72. doi: 10.1002/ijc.20060.
• [3] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [8] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [9] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [10] Improved apoptotic cell death in drug-resistant non-small-cell lung cancer cells by tumor necrosis factor-related apoptosis-inducing ligand-based treatment. J Pharmacol Exp Ther. 2014 Mar;348(3):360-71. doi: 10.1124/jpet.113.210054. Epub 2013 Dec 17.
• [11] 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.
• [12] 4-HPR modulates gene expression in ovarian cells. Int J Cancer. 2006 Sep 1;119(5):1005-13. doi: 10.1002/ijc.21797.
• [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] 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.