Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFIYC6Y)

• DOT Name: Putative protein-lysine deacylase ABHD14B (ABHD14B)
• Synonyms: EC 2.3.1.-; Alpha/beta hydrolase domain-containing protein 14B; Abhydrolase domain-containing protein 14B; CCG1-interacting factor B
• Gene Name: ABHD14B
• Related Disease:
  Breast cancer
  Breast carcinoma
  Metastatic malignant neoplasm
• UniProt ID: ABHEB_HUMAN
• PDB ID: 1IMJ
• EC Number: 2.3.1.-
• Pfam ID: PF12697
• Sequence:
  MAASVEQREGTIQVQGQALFFREALPGSGQARFSVLLLHGIRFSSETWQNLGTLHRLAQA
  GYRAVAIDLPGLGHSKEAAAPAPIGELAPGSFLAAVVDALELGPPVVISPSLSGMYSLPF
  LTAPGSQLPGFVPVAPICTDKINAANYASVKTPALIVYGDQDPMGQTSFEHLKQLPNHRV
  LIMKGAGHPCYLDKPEEWHTGLLDFLQGLQ
• Function: Acts as an atypical protein-lysine deacetylase in vitro. Catalyzes the deacetylation of lysine residues using CoA as substrate, generating acetyl-CoA and the free amine of protein-lysine residues. Additional experiments are however required to confirm the protein-lysine deacetylase activity in vivo (Probable). Has hydrolase activity towards various surrogate p-nitrophenyl (pNp) substrates, such as pNp-butyrate, pNp-acetate and pNp-octanoate in vitro, with a strong preference for pNp-acetate. May activate transcription.
• Tissue Specificity: Ubiquitous . Detected in spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood leukocyte, heart, placenta, lung, liver, skeletal muscle, pancreas and kidney .
• Reactome Pathway: Cytosolic sulfonation of small molecules (R-HSA-156584)
• BioCyc Pathway: MetaCyc:ENSG00000114779-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[11]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[17]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Putative protein-lysine deacylase ABHD14B (ABHD14B).	[18]

References

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• [2] Localization of sporadic neuroendocrine tumors by gene expression analysis of their metastases.Clin Exp Metastasis. 2011 Oct;28(7):637-47. doi: 10.1007/s10585-011-9397-5. Epub 2011 Jun 17.
• [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] 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.
• [5] 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.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [10] 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.
• [11] 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.
• [12] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [13] 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.
• [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] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [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] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [18] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.