Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM3INJN)

• DOT Name: Mediator of RNA polymerase II transcription subunit 30 (MED30)
• Synonyms: Mediator complex subunit 30; TRAP/Mediator complex component TRAP25; Thyroid hormone receptor-associated protein 6; Thyroid hormone receptor-associated protein complex 25 kDa component; Trap25
• Gene Name: MED30
• Related Disease:
  Bladder cancer
  Breast carcinoma
  Clear cell renal carcinoma
  Neoplasm
  Transposition of the great arteries
  Urinary bladder cancer
  Urinary bladder neoplasm
  Advanced cancer
  Gastric cancer
  Stomach cancer
• UniProt ID: MED30_HUMAN
• PDB ID: 7EMF; 7ENA; 7ENC; 7ENJ; 7LBM; 7NVR; 8GXQ; 8GXS
• Pfam ID: PF11315
• Sequence:
  MSTPPLAASGMAPGPFAGPQAQQAAREVNTASLCRIGQETVQDIVYRTMEIFQLLRNMQL
  PNGVTYHTGTYQDRLTKLQDNLRQLSVLFRKLRLVYDKCNENCGGMDPIPVEQLIPYVEE
  DGSKNDDRAGPPRFASEERREIAEVNKKLKQKNQQLKQIMDQLRNLIWDINAMLAMRN
• Function: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.
• Tissue Specificity: Expressed in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle.
• KEGG Pathway: Thyroid hormone sig.ling pathway (hsa04919)
• Reactome Pathway:
  Generic Transcription Pathway (R-HSA-212436)
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  PPARA activates gene expression (R-HSA-1989781)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Transposition of the great arteries	DISPXJ8X	Strong	Biomarker	[3]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[1]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[4]
Gastric cancer	DISXGOUK	moderate	Biomarker	[4]
Stomach cancer	DISKIJSX	moderate	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Mediator of RNA polymerase II transcription subunit 30 (MED30).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mediator of RNA polymerase II transcription subunit 30 (MED30).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mediator of RNA polymerase II transcription subunit 30 (MED30).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Mediator of RNA polymerase II transcription subunit 30 (MED30).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Mediator of RNA polymerase II transcription subunit 30 (MED30).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Mediator of RNA polymerase II transcription subunit 30 (MED30).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Mediator of RNA polymerase II transcription subunit 30 (MED30).	[11]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Mediator of RNA polymerase II transcription subunit 30 (MED30).	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Mediator of RNA polymerase II transcription subunit 30 (MED30).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Mediator of RNA polymerase II transcription subunit 30 (MED30).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Mediator of RNA polymerase II transcription subunit 30 (MED30).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Mediator of RNA polymerase II transcription subunit 30 (MED30).	[15]

References

• [1] The Contrasting Role of the Mediator Subunit MED30 in the Progression of Bladder Cancer.Anticancer Res. 2017 Dec;37(12):6685-6695. doi: 10.21873/anticanres.12127.
• [2] The knockdown of the mediator complex subunit MED30 suppresses the proliferation and migration of renal cell carcinoma cells.Ann Diagn Pathol. 2018 Jun;34:18-26. doi: 10.1016/j.anndiagpath.2017.12.008. Epub 2017 Dec 20.
• [3] Increasing evidence of pathogenic role of the Mediator (MED) complex in the development of cardiovascular diseases.Biochimie. 2019 Oct;165:1-8. doi: 10.1016/j.biochi.2019.06.014. Epub 2019 Jun 27.
• [4] MED30 Regulates the Proliferation and Motility of Gastric Cancer Cells.PLoS One. 2015 Jun 25;10(6):e0130826. doi: 10.1371/journal.pone.0130826. eCollection 2015.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] 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.
• [10] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [11] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [12] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.