Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG98AB1)

• DOT Name: Protein ABHD15 (ABHD15)
• Synonyms: Alpha/beta hydrolase domain-containing protein 15; Abhydrolase domain-containing protein 15
• Gene Name: ABHD15
• Related Disease:
  Obesity
  Type-1/2 diabetes
• UniProt ID: ABH15_HUMAN
• Sequence:
  MPPWGAALALILAVLALLGLLGPRLRGPWGRAVGERTLPGAQDRDDGEEADGGGPADQFS
  DGREPLPGGCSLVCKPSALAQCLLRALRRSEALEAGPRSWFSGPHLQTLCHFVLPVAPGP
  ELAREYLQLADDGLVALDWVVGPCVRGRRITSAGGLPAVLLVIPNAWGRLTRNVLGLCLL
  ALERGYYPVIFHRRGHHGCPLVSPRLQPFGDPSDLKEAVTYIRFRHPAAPLFAVSEGSGS
  ALLLSYLGECGSSSYVTGAACISPVLRCREWFEAGLPWPYERGFLLHQKIALSRYATALE
  DTVDTSRLFRSRSLREFEEALFCHTKSFPISWDTYWDRNDPLRDVDEAAVPVLCICSADD
  PVCGPPDHTLTTELFHSNPYFFLLLSRHGGHCGFLRQEPLPAWSHEVILESFRALTEFFR
  TEERIKGLSRHRASFLGGRRRGGALQRREVSSSSNLEEIFNWKRSYTR
• Function: May regulate adipocyte lipolysis and liver lipid accumulation.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Obesity	DIS47Y1K	Strong	Biomarker	[1]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[1]

2 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 Protein ABHD15 (ABHD15).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein ABHD15 (ABHD15).	[10]

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 Protein ABHD15 (ABHD15).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein ABHD15 (ABHD15).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein ABHD15 (ABHD15).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protein ABHD15 (ABHD15).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein ABHD15 (ABHD15).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein ABHD15 (ABHD15).	[6]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Protein ABHD15 (ABHD15).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein ABHD15 (ABHD15).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein ABHD15 (ABHD15).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein ABHD15 (ABHD15).	[12]

References

• [1] Loss of ABHD15 Impairs the Anti-lipolytic Action of Insulin by Altering PDE3B Stability and Contributes to Insulin Resistance.Cell Rep. 2018 May 15;23(7):1948-1961. doi: 10.1016/j.celrep.2018.04.055.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [9] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [10] 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.
• [11] 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.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.