Details of Drug Off-Target (DOT)

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

• DOT Name: Mediator of RNA polymerase II transcription subunit 20 (MED20)
• Synonyms: Mediator complex subunit 20; TRF-proximal protein homolog; hTRFP
• Gene Name: MED20
• Related Disease:
  Advanced cancer
  Neoplasm
• UniProt ID: MED20_HUMAN
• PDB ID: 7EMF; 7ENA; 7ENC; 7ENJ; 7LBM; 7NVR; 8GXQ; 8GXS
• Pfam ID: PF08612
• Sequence:
  MGVTCVSQMPVAEGKSVQQTVELLTRKLEMLGAEKQGTFCVDCETYHTAASTLGSQGQTG
  KLMYVMHNSEYPLSCFALFENGPCLIADTNFDVLMVKLKGFFQSAKASKIETRGTRYQYC
  DFLVKVGTVTMGPSARGISVEVEYGPCVVASDCWSLLLEFLQSFLGSHTPGAPAVFGNRH
  DAVYGPADTMVQYMELFNKIRKQQQVPVAGIR
• 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.
• 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

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Mediator of RNA polymerase II transcription subunit 20 (MED20).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mediator of RNA polymerase II transcription subunit 20 (MED20).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Mediator of RNA polymerase II transcription subunit 20 (MED20).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Mediator of RNA polymerase II transcription subunit 20 (MED20).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mediator of RNA polymerase II transcription subunit 20 (MED20).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Mediator of RNA polymerase II transcription subunit 20 (MED20).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Mediator of RNA polymerase II transcription subunit 20 (MED20).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Mediator of RNA polymerase II transcription subunit 20 (MED20).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Mediator of RNA polymerase II transcription subunit 20 (MED20).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Mediator of RNA polymerase II transcription subunit 20 (MED20).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mediator of RNA polymerase II transcription subunit 20 (MED20).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Mediator of RNA polymerase II transcription subunit 20 (MED20).	[13]

References

• [1] Gene expression profile of the whole Mediator complex in human osteosarcoma and normal osteoblasts.Med Oncol. 2013 Dec;30(4):739. doi: 10.1007/s12032-013-0739-9. Epub 2013 Oct 8.
• [2] Clinical significance of microRNAs in chronic and acute human leukemia.Mol Cancer. 2016 May 14;15(1):37. doi: 10.1186/s12943-016-0518-2.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] 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.
• [9] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.