Details of Drug Off-Target (DOT)

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

• DOT Name: Transcription factor E2F1 (E2F1)
• Synonyms: E2F-1; PBR3; Retinoblastoma-associated protein 1; RBAP-1; Retinoblastoma-binding protein 3; RBBP-3; pRB-binding protein E2F-1
• Gene Name: E2F1
• UniProt ID: E2F1_HUMAN
• PDB ID: 1H24; 1O9K; 2AZE; 5M9N; 5M9O; 6G0P; 6ULS
• Pfam ID: PF16421 ; PF02319
• Sequence:
  MALAGAPAGGPCAPALEALLGAGALRLLDSSQIVIISAAQDASAPPAPTGPAAPAAGPCD
  PDLLLFATPQAPRPTPSAPRPALGRPPVKRRLDLETDHQYLAESSGPARGRGRHPGKGVK
  SPGEKSRYETSLNLTTKRFLELLSHSADGVVDLNWAAEVLKVQKRRIYDITNVLEGIQLI
  AKKSKNHIQWLGSHTTVGVGGRLEGLTQDLRQLQESEQQLDHLMNICTTQLRLLSEDTDS
  QRLAYVTCQDLRSIADPAEQMVMVIKAPPETQLQAVDSSENFQISLKSKQGPIDVFLCPE
  ETVGGISPGKTPSQEVTSEEENRATDSATIVSPPPSSPPSSLTTDPSQSLLSLEQEPLLS
  RMGSLRAPVDEDRLSPLVAADSLLEHVREDFSGLLPEEFISLSPPHEALDYHFGLEEGEG
  IRDLFDCDFGDLTPLDF
• Function: Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase. E2F1 binds preferentially RB1 in a cell-cycle dependent manner. It can mediate both cell proliferation and TP53/p53-dependent apoptosis. Blocks adipocyte differentiation by binding to specific promoters repressing CEBPA binding to its target gene promoters. Directly activates transcription of PEG10. Positively regulates transcription of RRP1B.
• KEGG Pathway:
  Endocrine resistance (hsa01522)
  Cell cycle (hsa04110)
  Mitophagy - animal (hsa04137)
  Cellular senescence (hsa04218)
  Cushing syndrome (hsa04934)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Human cytomegalovirus infection (hsa05163)
  Human papillomavirus infection (hsa05165)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Epstein-Barr virus infection (hsa05169)
  Pathways in cancer (hsa05200)
  MicroR.s in cancer (hsa05206)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Pancreatic cancer (hsa05212)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Melanoma (hsa05218)
  Bladder cancer (hsa05219)
  Chronic myeloid leukemia (hsa05220)
  Small cell lung cancer (hsa05222)
  Non-small cell lung cancer (hsa05223)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  Inhibition of replication initiation of damaged DNA by RB1/E2F1 (R-HSA-113501)
  Transcription of E2F targets under negative control by DREAM complex (R-HSA-1362277)
  Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 (R-HSA-1362300)
  Activation of PUMA and translocation to mitochondria (R-HSA-139915)
  Pre-NOTCH Transcription and Translation (R-HSA-1912408)
  Oxidative Stress Induced Senescence (R-HSA-2559580)
  Oncogene Induced Senescence (R-HSA-2559585)
  TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest (R-HSA-6804116)
  G2 Phase (R-HSA-68911)
  Cyclin E associated events during G1/S transition (R-HSA-69202)
  G1/S-Specific Transcription (R-HSA-69205)
  Cyclin D associated events in G1 (R-HSA-69231)
  Cyclin A (R-HSA-69656)
  Transcriptional Regulation by E2F6 (R-HSA-8953750)
  Transcriptional regulation of granulopoiesis (R-HSA-9616222)
  Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) (R-HSA-9661069)
  Activation of NOXA and translocation to mitochondria (R-HSA-111448)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Transcription factor E2F1 (E2F1) increases the response to substance of Paclitaxel.	[61]
Vinblastine	DM5TVS3	Approved	Transcription factor E2F1 (E2F1) increases the response to substance of Vinblastine.	[61]

1 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 Transcription factor E2F1 (E2F1).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor E2F1 (E2F1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transcription factor E2F1 (E2F1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription factor E2F1 (E2F1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transcription factor E2F1 (E2F1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transcription factor E2F1 (E2F1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription factor E2F1 (E2F1).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Transcription factor E2F1 (E2F1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Transcription factor E2F1 (E2F1).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Transcription factor E2F1 (E2F1).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Transcription factor E2F1 (E2F1).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transcription factor E2F1 (E2F1).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Transcription factor E2F1 (E2F1).	[12]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Transcription factor E2F1 (E2F1).	[13]
Selenium	DM25CGV	Approved	Selenium increases the expression of Transcription factor E2F1 (E2F1).	[14]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Transcription factor E2F1 (E2F1).	[15]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Transcription factor E2F1 (E2F1).	[16]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Transcription factor E2F1 (E2F1).	[17]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Transcription factor E2F1 (E2F1).	[18]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Transcription factor E2F1 (E2F1).	[19]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Transcription factor E2F1 (E2F1).	[20]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Transcription factor E2F1 (E2F1).	[21]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Transcription factor E2F1 (E2F1).	[22]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Transcription factor E2F1 (E2F1).	[12]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Transcription factor E2F1 (E2F1).	[23]
DTI-015	DMXZRW0	Approved	DTI-015 increases the expression of Transcription factor E2F1 (E2F1).	[24]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Transcription factor E2F1 (E2F1).	[25]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of Transcription factor E2F1 (E2F1).	[6]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Transcription factor E2F1 (E2F1).	[26]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Transcription factor E2F1 (E2F1).	[27]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of Transcription factor E2F1 (E2F1).	[28]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Transcription factor E2F1 (E2F1).	[29]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Transcription factor E2F1 (E2F1).	[30]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Transcription factor E2F1 (E2F1).	[30]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Transcription factor E2F1 (E2F1).	[6]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of Transcription factor E2F1 (E2F1).	[6]
Gefitinib	DM15F0X	Approved	Gefitinib decreases the expression of Transcription factor E2F1 (E2F1).	[31]
Ritonavir	DMU764S	Approved	Ritonavir decreases the expression of Transcription factor E2F1 (E2F1).	[32]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of Transcription factor E2F1 (E2F1).	[6]
Ardeparin	DMYRX8B	Approved	Ardeparin decreases the expression of Transcription factor E2F1 (E2F1).	[33]
Dihydroxyacetone	DMM1LG2	Approved	Dihydroxyacetone increases the expression of Transcription factor E2F1 (E2F1).	[34]
Amodiaquine	DME4RA8	Approved	Amodiaquine affects the expression of Transcription factor E2F1 (E2F1).	[35]
Cilostazol	DMZMSCT	Approved	Cilostazol decreases the expression of Transcription factor E2F1 (E2F1).	[36]
Trabectedin	DMG3Y89	Approved	Trabectedin increases the expression of Transcription factor E2F1 (E2F1).	[37]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transcription factor E2F1 (E2F1).	[38]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Transcription factor E2F1 (E2F1).	[39]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine decreases the expression of Transcription factor E2F1 (E2F1).	[40]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Transcription factor E2F1 (E2F1).	[41]
Flavopiridol	DMKSUOI	Phase 2	Flavopiridol decreases the expression of Transcription factor E2F1 (E2F1).	[42]
Salirasib	DMRSU4X	Phase 2	Salirasib decreases the expression of Transcription factor E2F1 (E2F1).	[43]
2-hydroxyoleic acid	DMCLKA4	Phase 1/2	2-hydroxyoleic acid decreases the expression of Transcription factor E2F1 (E2F1).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transcription factor E2F1 (E2F1).	[45]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transcription factor E2F1 (E2F1).	[46]
Eugenol	DM7US1H	Patented	Eugenol decreases the expression of Transcription factor E2F1 (E2F1).	[47]
Harmine	DMPA5WD	Patented	Harmine increases the expression of Transcription factor E2F1 (E2F1).	[48]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Transcription factor E2F1 (E2F1).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transcription factor E2F1 (E2F1).	[50]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Transcription factor E2F1 (E2F1).	[51]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Transcription factor E2F1 (E2F1).	[52]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Transcription factor E2F1 (E2F1).	[53]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Transcription factor E2F1 (E2F1).	[54]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Transcription factor E2F1 (E2F1).	[55]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Transcription factor E2F1 (E2F1).	[56]
AHPN	DM8G6O4	Investigative	AHPN increases the expression of Transcription factor E2F1 (E2F1).	[57]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of Transcription factor E2F1 (E2F1).	[2]
Oleic acid	DM54O1Z	Investigative	Oleic acid decreases the expression of Transcription factor E2F1 (E2F1).	[44]
27-hydroxycholesterol	DM2L6OZ	Investigative	27-hydroxycholesterol increases the expression of Transcription factor E2F1 (E2F1).	[58]
GW-3965	DMG60ET	Investigative	GW-3965 decreases the expression of Transcription factor E2F1 (E2F1).	[59]
Plumbagin	DM9BS50	Investigative	Plumbagin decreases the expression of Transcription factor E2F1 (E2F1).	[60]
NSC-654077	DMW3QAK	Investigative	NSC-654077 decreases the expression of Transcription factor E2F1 (E2F1).	[7]

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