Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMKVO0J)

• DOT Name: Bcl-2-like protein 2 (BCL2L2)
• Synonyms: Bcl2-L-2; Apoptosis regulator Bcl-W
• Gene Name: BCL2L2
• UniProt ID: B2CL2_HUMAN
• PDB ID: 1MK3; 1O0L; 1ZY3; 2Y6W; 4CIM
• Pfam ID: PF00452 ; PF02180
• Sequence:
  MATPASAPDTRALVADFVGYKLRQKGYVCGAGPGEGPAADPLHQAMRAAGDEFETRFRRT
  FSDLAAQLHVTPGSAQQRFTQVSDELFQGGPNWGRLVAFFVFGAALCAESVNKEMEPLVG
  QVQEWMVAYLETQLADWIHSSGGWAEFTALYGDGALEEARRLREGNWASVRTVLTGAVAL
  GALVTVGAFFASK
• Function: Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX.
• Tissue Specificity: Expressed (at protein level) in a wide range of tissues with highest levels in brain, spinal cord, testis, pancreas, heart, spleen and mammary glands. Moderate levels found in thymus, ovary and small intestine. Not detected in salivary gland, muscle or liver. Also expressed in cell lines of myeloid, fibroblast and epithelial origin. Not detected in most lymphoid cell lines.
• KEGG Pathway: MicroR.s in cancer (hsa05206)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Bcl-2-like protein 2 (BCL2L2) decreases the response to substance of Etoposide.	[22]

1 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 Bcl-2-like protein 2 (BCL2L2).	[1]

21 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 Bcl-2-like protein 2 (BCL2L2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of Bcl-2-like protein 2 (BCL2L2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Bcl-2-like protein 2 (BCL2L2).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Bcl-2-like protein 2 (BCL2L2).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Bcl-2-like protein 2 (BCL2L2).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Bcl-2-like protein 2 (BCL2L2).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Bcl-2-like protein 2 (BCL2L2).	[8]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Bcl-2-like protein 2 (BCL2L2).	[9]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Bcl-2-like protein 2 (BCL2L2).	[10]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Bcl-2-like protein 2 (BCL2L2).	[11]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Bcl-2-like protein 2 (BCL2L2).	[12]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Bcl-2-like protein 2 (BCL2L2).	[13]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Bcl-2-like protein 2 (BCL2L2).	[14]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Bcl-2-like protein 2 (BCL2L2).	[15]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Bcl-2-like protein 2 (BCL2L2).	[16]
PF-3758309	DM36PKZ	Phase 1	PF-3758309 increases the expression of Bcl-2-like protein 2 (BCL2L2).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Bcl-2-like protein 2 (BCL2L2).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Bcl-2-like protein 2 (BCL2L2).	[19]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Bcl-2-like protein 2 (BCL2L2).	[20]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Bcl-2-like protein 2 (BCL2L2).	[4]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Bcl-2-like protein 2 (BCL2L2).	[21]

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] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [4] Differential effect of methyl-, butyl- and propylparaben and 17-estradiol on selected cell cycle and apoptosis gene and protein expression in MCF-7 breast cancer cells and MCF-10A non-malignant cells. J Appl Toxicol. 2014 Sep;34(9):1041-50. doi: 10.1002/jat.2978. Epub 2014 Jan 30.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Curcumin reduces the expression of survivin, leading to enhancement of arsenic trioxide-induced apoptosis in myelodysplastic syndrome and leukemia stem-like cells. Oncol Rep. 2016 Sep;36(3):1233-42. doi: 10.3892/or.2016.4944. Epub 2016 Jul 15.
• [7] Gene expression changes in human small airway epithelial cells exposed to Delta9-tetrahydrocannabinol. Toxicol Lett. 2005 Aug 14;158(2):95-107.
• [8] 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.
• [9] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [10] Niclosamide overcomes acquired resistance to erlotinib through suppression of STAT3 in non-small cell lung cancer. Mol Cancer Ther. 2013 Oct;12(10):2200-12. doi: 10.1158/1535-7163.MCT-13-0095. Epub 2013 Jul 26.
• [11] [Inducing-apoptosis effect of bortezomib on acute monocytic leukemia cell SHI-1 and its influence on expressions of Bcl2l12, Bcl-2 and Bax genes]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Oct;16(5):1016-20.
• [12] Activation of peroxisome proliferator-activated receptor-gamma by troglitazone (TGZ) inhibits human lung cell growth. J Cell Biochem. 2005 Nov 1;96(4):760-74. doi: 10.1002/jcb.20474.
• [13] 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.
• [14] Resveratrol induces nuclear factor-B activity in human cardiac cells. Int J Cardiol. 2013 Sep 10;167(6):2507-16. doi: 10.1016/j.ijcard.2012.06.006. Epub 2012 Jun 27.
• [15] Expression profiles of apoptotic genes induced by curcumin in human breast cancer and mammary epithelial cell lines. Anticancer Res. 2005 Sep-Oct;25(5):3293-302.
• [16] Copper chelator ATN-224 inhibits endothelial function by multiple mechanisms. Microvasc Res. 2009 May;77(3):314-26.
• [17] Inhibition of neuroblastoma proliferation by PF-3758309, a small-molecule inhibitor that targets p21-activated kinase 4. Oncol Rep. 2017 Nov;38(5):2705-2716. doi: 10.3892/or.2017.5989. Epub 2017 Sep 22.
• [18] 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.
• [19] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [20] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [21] Geraniol inhibits prostate cancer growth by targeting cell cycle and apoptosis pathways. Biochem Biophys Res Commun. 2011 Apr 1;407(1):129-34. doi: 10.1016/j.bbrc.2011.02.124. Epub 2011 Mar 1.
• [22] Alteration in copy numbers of genes as a mechanism for acquired drug resistance. Cancer Res. 2004 Feb 15;64(4):1403-10. doi: 10.1158/0008-5472.can-3263-2.