Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSZCFD8)

• DOT Name: Ankyrin repeat domain-containing protein 65 (ANKRD65)
• Gene Name: ANKRD65
• UniProt ID: ANR65_HUMAN
• Pfam ID: PF12796 ; PF13637
• Sequence:
  MDSQRPEPREEEEEEQELRWMELDSEEALGTRTEGPSVVQGWGHLLQAVWRGPAGLVTQL
  LRQGASVEERDHAGRTPLHLAVLRGHAPLVRLLLQRGAPVGAVDRAGRTALHEAAWHGHS
  RVAELLLQRGASAAARSGTGLTPLHWAAALGHTLLAARLLEAPGPGPAAAEAEDARGWTA
  AHWAAAGGRLAVLELLAAGGAGLDGALLVAAAAGRGAALRFLLARGARVDARDGAGATAL
  GLAAALGRSQDIEVLLGHGADPGIRDRHGRSALHRAAARGHLLAVQLLVTQGAEVDARDT
  LGLTPLHHASREGHVEVAGCLLDRGAQVDATGWLRKTPLHLAAERGHGPTVGLLLSRGAS
  PTLRTQWAEVAQMPEGDLPQALPELGGGEKECEGIESTG

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 increases the methylation of Ankyrin repeat domain-containing protein 65 (ANKRD65).	[1]

6 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 Ankyrin repeat domain-containing protein 65 (ANKRD65).	[2]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Ankyrin repeat domain-containing protein 65 (ANKRD65).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ankyrin repeat domain-containing protein 65 (ANKRD65).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ankyrin repeat domain-containing protein 65 (ANKRD65).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Ankyrin repeat domain-containing protein 65 (ANKRD65).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Ankyrin repeat domain-containing protein 65 (ANKRD65).	[7]

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] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [7] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.