Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOO24C4)

• DOT Name: Mediator of RNA polymerase II transcription subunit 1 (MED1)
• Synonyms: Activator-recruited cofactor 205 kDa component; ARC205; Mediator complex subunit 1; Peroxisome proliferator-activated receptor-binding protein; PBP; PPAR-binding protein; Thyroid hormone receptor-associated protein complex 220 kDa component; Trap220; Thyroid receptor-interacting protein 2; TR-interacting protein 2; TRIP-2; Vitamin D receptor-interacting protein complex component DRIP205; p53 regulatory protein RB18A
• Gene Name: MED1
• Related Disease:
  Melanoma
  Acute intermittent hepatic porphyria
  Acute otitis media
  Arteriosclerosis
  Asthma
  Atherosclerosis
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Bullous pemphigoid
  Colon cancer
  Colorectal carcinoma
  Dilated cardiomyopathy
  Endometriosis
  Epilepsy
  Familial Alzheimer disease
  Gastric cancer
  Hepatocellular carcinoma
  Influenza
  Non-small-cell lung cancer
  Pancreatic cancer
  Primary biliary cholangitis
  Prostate adenocarcinoma
  Prostate carcinoma
  Stomach cancer
  Synovial sarcoma
  Systemic lupus erythematosus
  Thyroid gland undifferentiated (anaplastic) carcinoma
  Triple negative breast cancer
  Adenocarcinoma
  Advanced cancer
  Bone osteosarcoma
  Lung adenocarcinoma
  Osteosarcoma
  Prostate cancer
  Acute myelogenous leukaemia
  Bladder cancer
  Glioma
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Parkinson disease
  Streptococcal pneumonia
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: MED1_HUMAN
• PDB ID: 1RJK ; 1RK3 ; 1RKG ; 1RKH ; 2O4J ; 2O4R ; 2ZFX ; 3A2H ; 3AUN ; 3VJS ; 3VJT ; 3VRT ; 3VRU ; 3VRV ; 3VRW ; 3W0G ; 3W0H ; 3W0I ; 3W0J ; 3W5P ; 3W5Q ; 3W5R ; 3W5T ; 3WT5 ; 3WT6 ; 3WT7 ; 3WTQ ; 4YNK ; 5AWJ ; 5AWK ; 5B41 ; 5B5B ; 5GIC ; 5GID ; 5GIE ; 5XPM ; 5XPN ; 5XPO ; 5XPP ; 5XUQ ; 5XZF ; 5XZH ; 5ZWE ; 5ZWF ; 5ZWH ; 5ZWI ; 6D94 ; 6JEZ ; 6K5O ; 6ONJ ; 7C7V ; 7C7W ; 7EMF ; 7ENA ; 7ENC ; 7ENJ ; 7OXU ; 7VQP ; 8GXQ ; 8GXS
• Pfam ID: PF10744
• Sequence:
  MKAQGETEESEKLSKMSSLLERLHAKFNQNRPWSETIKLVRQVMEKRVVMSSGGHQHLVS
  CLETLQKALKVTSLPAMTDRLESIARQNGLGSHLSASGTECYITSDMFYVEVQLDPAGQL
  CDVKVAHHGENPVSCPELVQQLREKNFDEFSKHLKGLVNLYNLPGDNKLKTKMYLALQSL
  EQDLSKMAIMYWKATNAGPLDKILHGSVGYLTPRSGGHLMNLKYYVSPSDLLDDKTASPI
  ILHENNVSRSLGMNASVTIEGTSAVYKLPIAPLIMGSHPVDNKWTPSFSSITSANSVDLP
  ACFFLKFPQPIPVSRAFVQKLQNCTGIPLFETQPTYAPLYELITQFELSKDPDPIPLNHN
  MRFYAALPGQQHCYFLNKDAPLPDGRSLQGTLVSKITFQHPGRVPLILNLIRHQVAYNTL
  IGSCVKRTILKEDSPGLLQFEVCPLSESRFSVSFQHPVNDSLVCVVMDVQDSTHVSCKLY
  KGLSDALICTDDFIAKVVQRCMSIPVTMRAIRRKAETIQADTPALSLIAETVEDMVKKNL
  PPASSPGYGMTTGNNPMSGTTTPTNTFPGGPITTLFNMSMSIKDRHESVGHGEDFSKVSQ
  NPILTSLLQITGNGGSTIGSSPTPPHHTPPPVSSMAGNTKNHPMLMNLLKDNPAQDFSTL
  YGSSPLERQNSSSGSPRMEICSGSNKTKKKKSSRLPPEKPKHQTEDDFQRELFSMDVDSQ
  NPIFDVNMTADTLDTPHITPAPSQCSTPPTTYPQPVPHPQPSIQRMVRLSSSDSIGPDVT
  DILSDIAEEASKLPSTSDDCPAIGTPLRDSSSSGHSQSTLFDSDVFQTNNNENPYTDPAD
  LIADAAGSPSSDSPTNHFFHDGVDFNPDLLNSQSQSGFGEEYFDESSQSGDNDDFKGFAS
  QALNTLGVPMLGGDNGETKFKGNNQADTVDFSIISVAGKALAPADLMEHHSGSQGPLLTT
  GDLGKEKTQKRVKEGNGTSNSTLSGPGLDSKPGKRSRTPSNDGKSKDKPPKRKKADTEGK
  SPSHSSSNRPFTPPTSTGGSKSPGSAGRSQTPPGVATPPIPKITIQIPKGTVMVGKPSSH
  SQYTSSGSVSSSGSKSHHSHSSSSSSSASTSGKMKSSKSEGSSSSKLSSSMYSSQGSSGS
  SQSKNSSQSGGKPGSSPITKHGLSSGSSSTKMKPQGKPSSLMNPSLSKPNISPSHSRPPG
  GSDKLASPMKPVPGTPPSSKAKSPISSGSGGSHMSGTSSSSGMKSSSGLGSSGSLSQKTP
  PSSNSCTASSSSFSSSGSSMSSSQNQHGSSKGKSPSRNKKPSLTAVIDKLKHGVVTSGPG
  GEDPLDGQMGVSTNSSSHPMSSKHNMSGGEFQGKREKSDKDKSKVSTSGSSVDSSKKTSE
  SKNVGSTGVAKIIISKHDGGSPSIKAKVTLQKPGESSGEGLRPQMASSKNYGSPLISGST
  PKHERGSPSHSKSPAYTPQNLDSESESGSSIAEKSYQNSPSSDDGIRPLPEYSTEKHKKH
  KKEKKKVKDKDRDRDRDKDRDKKKSHSIKPESWSKSPISSDQSLSMTSNTILSADRPSRL
  SPDFMIGEEDDDLMDVALIGN
• 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. Acts as a coactivator for GATA1-mediated transcriptional activation during erythroid differentiation of K562 erythroleukemia cells.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway:
  Endocrine resistance (hsa01522)
  Thyroid hormone sig.ling pathway (hsa04919)
• Reactome Pathway:
  BMAL1 (R-HSA-1368108)
  PPARA activates gene expression (R-HSA-1989781)
  Generic Transcription Pathway (R-HSA-212436)
  Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201)
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  Nuclear Receptor transcription pathway (R-HSA-383280)
  Regulation of lipid metabolism by PPARalpha (R-HSA-400206)
  Circadian Clock (R-HSA-400253)
  Estrogen-dependent gene expression (R-HSA-9018519)
  Cytoprotection by HMOX1 (R-HSA-9707564)
  Heme signaling (R-HSA-9707616)
  RORA activates gene expression (R-HSA-1368082)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Definitive	Biomarker	[1]
Acute intermittent hepatic porphyria	DIS80J7E	Strong	Biomarker	[2]
Acute otitis media	DISL8D8G	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[4]
Asthma	DISW9QNS	Strong	Genetic Variation	[5]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Bullous pemphigoid	DISOJLKV	Strong	Biomarker	[8]
Colon cancer	DISVC52G	Strong	Genetic Variation	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[10]
Dilated cardiomyopathy	DISX608J	Strong	Altered Expression	[11]
Endometriosis	DISX1AG8	Strong	Biomarker	[12]
Epilepsy	DISBB28L	Strong	Altered Expression	[13]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[14]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[15]
Influenza	DIS3PNU3	Strong	Genetic Variation	[16]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[17]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[18]
Primary biliary cholangitis	DIS43E0O	Strong	Genetic Variation	[19]
Prostate adenocarcinoma	DISBZYU8	Strong	Altered Expression	[20]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[21]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[9]
Synovial sarcoma	DISEZJS7	Strong	Altered Expression	[22]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[23]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Strong	Altered Expression	[24]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[25]
Adenocarcinoma	DIS3IHTY	moderate	Altered Expression	[26]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[27]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[28]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[26]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[28]
Prostate cancer	DISF190Y	Disputed	Biomarker	[21]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[29]
Bladder cancer	DISUHNM0	Limited	Altered Expression	[1]
Glioma	DIS5RPEH	Limited	Biomarker	[30]
Lung cancer	DISCM4YA	Limited	Biomarker	[1]
Lung carcinoma	DISTR26C	Limited	Biomarker	[1]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[1]
Parkinson disease	DISQVHKL	Limited	Biomarker	[31]
Streptococcal pneumonia	DIS2EKMJ	Limited	Genetic Variation	[32]
Urinary bladder cancer	DISDV4T7	Limited	Altered Expression	[1]
Urinary bladder neoplasm	DIS7HACE	Limited	Altered Expression	[1]

13 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 Mediator of RNA polymerase II transcription subunit 1 (MED1).	[33]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[36]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[37]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[38]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[40]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[37]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[42]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[43]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[44]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[46]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[47]

5 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin affects the phosphorylation of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[45]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[39]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[39]
PD98059	DMZC90M	Investigative	PD98059 decreases the phosphorylation of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[48]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the binding of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[41]
PMID25416646-Compound-Figure2-K	DMNTAYK	Patented	PMID25416646-Compound-Figure2-K affects the binding of Mediator of RNA polymerase II transcription subunit 1 (MED1).	[41]

References

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