Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4UCBG5)

• DOT Name: Indoleamine 2,3-dioxygenase 2 (IDO2)
• Synonyms: IDO-2; EC 1.13.11.-; Indoleamine 2,3-dioxygenase-like protein 1; Indoleamine-pyrrole 2,3-dioxygenase-like protein 1
• Gene Name: IDO2
• UniProt ID: I23O2_HUMAN
• EC Number: 1.13.11.-
• Pfam ID: PF01231
• Sequence:
  MEPHRPNVKTAVPLSLESYHISEEYGFLLPDSLKELPDHYRPWMEIANKLPQLIDAHQLQ
  AHVDKMPLLSCQFLKGHREQRLAHLVLSFLTMGYVWQEGEAQPAEVLPRNLALPFVEVSR
  NLGLPPILVHSDLVLTNWTKKDPDGFLEIGNLETIISFPGGESLHGFILVTALVEKEAVP
  GIKALVQATNAILQPNQEALLQALQRLRLSIQDITKTLGQMHDYVDPDIFYAGIRIFLSG
  WKDNPAMPAGLMYEGVSQEPLKYSGGSAAQSTVLHAFDEFLGIRHSKESGDFLYRMRDYM
  PPSHKAFIEDIHSAPSLRDYILSSGQDHLLTAYNQCVQALAELRSYHITMVTKYLITAAA
  KAKHGKPNHLPGPPQALKDRGTGGTAVMSFLKSVRDKTLESILHPRG
• Function: Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway. Involved in immune regulation. May not play a significant role in tryptophan-related tumoral resistance.
• Tissue Specificity: Detected in liver, small intestine, spleen, placenta, thymus, lung, brain, kidney, and colon . Also expressed at low level in testis and thyroid. Not expressed in the majority of human tumor samples (>99%) .
• KEGG Pathway:
  Tryptophan metabolism (hsa00380)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
  African trypanosomiasis (hsa05143)
• Reactome Pathway: Tryptophan catabolism (R-HSA-71240)

Molecular Interaction Atlas (MIA) of This DOT

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 Indoleamine 2,3-dioxygenase 2 (IDO2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Indoleamine 2,3-dioxygenase 2 (IDO2).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Indoleamine 2,3-dioxygenase 2 (IDO2).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Indoleamine 2,3-dioxygenase 2 (IDO2).	[4]

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] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [3] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [4] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.