Details of Drug Off-Target (DOT)

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

• DOT Name: Alpha/beta hydrolase domain-containing protein 17B (ABHD17B)
• Synonyms: Abhydrolase domain-containing protein 17B; EC 3.1.2.22
• Gene Name: ABHD17B
• UniProt ID: AB17B_HUMAN
• EC Number: 3.1.2.22
• Pfam ID: PF12146
• Sequence:
  MNNLSFSELCCLFCCPPCPGKIASKLAFLPPDPTYTLMCDESGSRWTLHLSERADWQYSS
  REKDAIECFMTRTSKGNRIACMFVRCSPNAKYTLLFSHGNAVDLGQMSSFYIGLGSRINC
  NIFSYDYSGYGASSGKPTEKNLYADIEAAWLALRTRYGIRPENVIIYGQSIGTVPSVDLA
  ARYESAAVILHSPLTSGMRVAFPDTKKTYCFDAFPNIDKISKITSPVLIIHGTEDEVIDF
  SHGLALFERCQRPVEPLWVEGAGHNDVELYGQYLERLKQFVSQELVNL
• Function: Hydrolyzes fatty acids from S-acylated cysteine residues in proteins. Has depalmitoylating activity towards DLG4/PSD95. Has depalmitoylating activity towards GAP43. Has depalmitoylating activity towards MAP6. Has depalmitoylating activity towards NRAS.
• Reactome Pathway: RAS processing (R-HSA-9648002)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Alpha/beta hydrolase domain-containing protein 17B (ABHD17B).	[1]

10 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 Alpha/beta hydrolase domain-containing protein 17B (ABHD17B).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Alpha/beta hydrolase domain-containing protein 17B (ABHD17B).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Alpha/beta hydrolase domain-containing protein 17B (ABHD17B).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Alpha/beta hydrolase domain-containing protein 17B (ABHD17B).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Alpha/beta hydrolase domain-containing protein 17B (ABHD17B).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Alpha/beta hydrolase domain-containing protein 17B (ABHD17B).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Alpha/beta hydrolase domain-containing protein 17B (ABHD17B).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Alpha/beta hydrolase domain-containing protein 17B (ABHD17B).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Alpha/beta hydrolase domain-containing protein 17B (ABHD17B).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Alpha/beta hydrolase domain-containing protein 17B (ABHD17B).	[11]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [10] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.