Details of Drug Off-Target (DOT)

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

• DOT Name: Interleukin-17D (IL17D)
• Synonyms: IL-17D; Interleukin-27; IL-27
• Gene Name: IL17D
• UniProt ID: IL17D_HUMAN
• Pfam ID: PF06083
• Sequence:
  MLVAGFLLALPPSWAAGAPRAGRRPARPRGCADRPEELLEQLYGRLAAGVLSAFHHTLQL
  GPREQARNASCPAGGRPADRRFRPPTNLRSVSPWAYRISYDPARYPRYLPEAYCLCRGCL
  TGLFGEEDVRFRSAPVYMPTVVLRRTPACAGGRSVYTEAYVTIPVGCTCVPEPEKDADSI
  NSSIDKQGAKLLLGPNDAPAGP
• Function: Induces expression of IL6, CXCL8/IL8, and CSF2/GM-CSF from endothelial cells.
• Tissue Specificity: Expressed preferentially in adipose, skeletal muscle and CNS.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  C-type lectin receptor sig.ling pathway (hsa04625)
  IL-17 sig.ling pathway (hsa04657)

Molecular Interaction Atlas (MIA) of This DOT

3 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 Interleukin-17D (IL17D).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Interleukin-17D (IL17D).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Interleukin-17D (IL17D).	[11]

9 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 Interleukin-17D (IL17D).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Interleukin-17D (IL17D).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interleukin-17D (IL17D).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interleukin-17D (IL17D).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Interleukin-17D (IL17D).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Interleukin-17D (IL17D).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Interleukin-17D (IL17D).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Interleukin-17D (IL17D).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Interleukin-17D (IL17D).	[10]

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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] 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.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] 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.