Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYXQJ3I)

• DOT Name: Bcl-2-like protein 10 (BCL2L10)
• Synonyms: Bcl2-L-10; Anti-apoptotic protein Boo; Anti-apoptotic protein NrH; Apoptosis regulator Bcl-B
• Gene Name: BCL2L10
• Related Disease:
  Acute leukaemia
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Attention deficit hyperactivity disorder
  B-cell lymphoma
  B-cell neoplasm
  Carcinoma
  Colorectal carcinoma
  Epithelial neoplasm
  Follicular lymphoma
  Gastric cancer
  Hepatocellular carcinoma
  Lung cancer
  Myelodysplastic syndrome
  Neoplasm
  Plasma cell myeloma
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
  Toxic epidermal necrolysis
  Tuberculosis
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Childhood myelodysplastic syndrome
• UniProt ID: B2L10_HUMAN
• PDB ID: 4B4S
• Pfam ID: PF00452
• Sequence:
  MVDQLRERTTMADPLRERTELLLADYLGYCAREPGTPEPAPSTPEAAVLRSAAARLRQIH
  RSFFSAYLGYPGNRFELVALMADSVLSDSPGPTWGRVVTLVTFAGTLLERGPLVTARWKK
  WGFQPRLKEQEGDVARDCQRLVALLSSRLMGQHRAWLQAQGGWDGFCHFFRTPFPLAFWR
  KQLVQAFLSCLLTTAFIYLWTRLL
• Function: Promotes cell survival by suppressing apoptosis induced by BAX but not BAK. Increases binding of AHCYL1/IRBIT to ITPR1. Reduces ITPR1-mediated calcium release from the endoplasmic reticulum cooperatively with AHCYL1/IRBIT under normal cellular conditions. Under apoptotic stress conditions, dissociates from ITPR1 and is displaced from mitochondria-associated endoplasmic reticulum membranes, leading to increased Ca(2+) transfer to mitochondria which promotes apoptosis. Required for the correct formation of the microtubule organizing center during oocyte cell division, potentially via regulation of protein abundance and localization of other microtubule organizing center components such as AURKA and TPX2.
• Tissue Specificity: Widely expressed in adult tissues. Preferentially expressed in lung, liver and kidney.

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute leukaemia	DISDQFDI	Strong	Posttranslational Modification	[1]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[4]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[5]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[6]
Carcinoma	DISH9F1N	Strong	Altered Expression	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[5]
Epithelial neoplasm	DIS0T594	Strong	Genetic Variation	[5]
Follicular lymphoma	DISVEUR6	Strong	Biomarker	[5]
Gastric cancer	DISXGOUK	Strong	Posttranslational Modification	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[9]
Lung cancer	DISCM4YA	Strong	Altered Expression	[5]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Altered Expression	[11]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[5]
Prostate cancer	DISF190Y	Strong	Altered Expression	[5]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[5]
Stomach cancer	DISKIJSX	Strong	Biomarker	[12]
Toxic epidermal necrolysis	DISIWPFR	Strong	Altered Expression	[6]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[13]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[7]
Breast cancer	DIS7DPX1	Limited	Biomarker	[7]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[7]
Childhood myelodysplastic syndrome	DISMN80I	Limited	Genetic Variation	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Bcl-2-like protein 10 (BCL2L10).	[14]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Bcl-2-like protein 10 (BCL2L10).	[15]
Zoledronate	DMIXC7G	Approved	Zoledronate affects the expression of Bcl-2-like protein 10 (BCL2L10).	[16]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Bcl-2-like protein 10 (BCL2L10).	[17]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Bcl-2-like protein 10 (BCL2L10).	[18]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Bcl-2-like protein 10 (BCL2L10).	[19]

References

• [1] Analysis of genome-wide methylation and gene expression induced by 5-aza-2'-deoxycytidine identifies BCL2L10 as a frequent methylation target in acute myeloid leukemia.Leuk Lymphoma. 2010 Dec;51(12):2275-84. doi: 10.3109/10428194.2010.528093. Epub 2010 Nov 15.
• [2] BCL2L10 is a predictive factor for resistance to azacitidine in MDS and AML patients.Oncotarget. 2012 Apr;3(4):490-501. doi: 10.18632/oncotarget.481.
• [3] BCL2L10 positive cells in bone marrow are an independent prognostic factor of azacitidine outcome in myelodysplastic syndrome and acute myeloid leukemia.Oncotarget. 2017 Jul 18;8(29):47103-47109. doi: 10.18632/oncotarget.17482.
• [4] Screening for adult attention-deficit/hyperactivity disorder in alcohol dependent patients: Underreporting of ADHD symptoms in self-report scales.Drug Alcohol Depend. 2019 Feb 1;195:52-58. doi: 10.1016/j.drugalcdep.2018.11.020. Epub 2018 Dec 10.
• [5] Bcl-B expression in human epithelial and nonepithelial malignancies.Clin Cancer Res. 2008 May 15;14(10):3011-21. doi: 10.1158/1078-0432.CCR-07-1955.
• [6] Upregulation of miR-18a-5p contributes to epidermal necrolysis in severe drug eruptions.J Allergy Clin Immunol. 2014 Apr;133(4):1065-74. doi: 10.1016/j.jaci.2013.09.019. Epub 2013 Nov 1.
• [7] Breast Cancer Targeting through Inhibition of the Endoplasmic Reticulum-Based Apoptosis Regulator Nrh/BCL2L10.Cancer Res. 2018 Mar 15;78(6):1404-1417. doi: 10.1158/0008-5472.CAN-17-0846. Epub 2018 Jan 12.
• [8] BCL2L10 is frequently silenced by promoter hypermethylation in gastric cancer.Oncol Rep. 2010 Jun;23(6):1701-8. doi: 10.3892/or_00000814.
• [9] MicroRNA-18a promotes hepatocellular carcinoma proliferation, migration, and invasion by targeting Bcl2L10.Onco Targets Ther. 2018 Nov 9;11:7919-7934. doi: 10.2147/OTT.S180971. eCollection 2018.
• [10] Clinical Outcomes of Decitabine Treatment for Patients With Lower-Risk Myelodysplastic Syndrome on the Basis of the International Prognostic Scoring System.Clin Lymphoma Myeloma Leuk. 2019 Oct;19(10):656-664. doi: 10.1016/j.clml.2019.06.003. Epub 2019 Jun 27.
• [11] BCLB, methylated in hepatocellular carcinoma, is a starvation stresssensor that induces apoptosis and autophagy through theAMPK-mTOR signaling cascade.Cancer Lett. 2017 Jun 1;395:63-71. doi: 10.1016/j.canlet.2017.02.030. Epub 2017 Mar 2.
• [12] BCL2L10 protein regulates apoptosis/proliferation through differential pathways in gastric cancer cells.J Pathol. 2011 Feb;223(3):400-9. doi: 10.1002/path.2811. Epub 2010 Nov 22.
• [13] Tuberculin Skin Testing Boosts Interferon Gamma Responses to DIVA Reagents in Mycobacterium bovis-Infected Cattle.Clin Vaccine Immunol. 2017 May 5;24(5):e00551-16. doi: 10.1128/CVI.00551-16. Print 2017 May.
• [14] 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.
• [15] Molecular mechanism of action of bisphenol and bisphenol A mediated by oestrogen receptor alpha in growth and apoptosis of breast cancer cells. Br J Pharmacol. 2013 May;169(1):167-78.
• [16] Effect of zoledronic acid on oral fibroblasts and epithelial cells: a potential mechanism of bisphosphonate-associated osteonecrosis. Br J Haematol. 2009 Mar;144(5):667-76. doi: 10.1111/j.1365-2141.2008.07504.x. Epub 2008 Nov 20.
• [17] 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.
• [18] 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.
• [19] Identification of genes associated with paraquat-induced toxicity in SH-SY5Y cells by PCR array focused on apoptotic pathways. J Toxicol Environ Health A. 2008;71(22):1457-67. doi: 10.1080/15287390802329364.