Details of Drug Off-Target (DOT)

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

• DOT Name: Retinoblastoma-like protein 1 (RBL1)
• Synonyms: 107 kDa retinoblastoma-associated protein; p107; pRb1
• Gene Name: RBL1
• Related Disease:
  B-cell neoplasm
  Prostate cancer
  Prostate carcinoma
  Adenoma
  Advanced cancer
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Endometrial carcinoma
  Fatty liver disease
  Head and neck cancer
  Head and neck carcinoma
  Hemangioblastoma
  Hepatitis C virus infection
  Lung cancer
  Lung carcinoma
  Neoplasm
  Prostate neoplasm
  Retinoblastoma
  Squamous cell carcinoma
  Cervical cancer
  Cervical carcinoma
• UniProt ID: RBL1_HUMAN
• PDB ID: 1H28; 4YOO; 4YOS; 4YOZ; 5TUV; 7SMC; 7SMD; 7SME; 7SMF
• Pfam ID: PF11934 ; PF01858 ; PF01857 ; PF08934
• Sequence:
  MFEDKPHAEGAAVVAAAGEALQALCQELNLDEGSAAEALDDFTAIRGNYSLEGEVTHWLA
  CSLYVACRKSIIPTVGKGIMEGNCVSLTRILRSAKLSLIQFFSKMKKWMDMSNLPQEFRE
  RIERLERNFEVSTVIFKKYEPIFLDIFQNPYEEPPKLPRSRKQRRIPCSVKDLFNFCWTL
  FVYTKGNFRMIGDDLVNSYHLLLCCLDLIFANAIMCPNRQDLLNPSFKGLPSDFHTADFT
  ASEEPPCIIAVLCELHDGLLVEAKGIKEHYFKPYISKLFDRKILKGECLLDLSSFTDNSK
  AVNKEYEEYVLTVGDFDERIFLGADAEEEIGTPRKFTRDTPLGKLTAQANVEYNLQQHFE
  KKRSFAPSTPLTGRRYLREKEAVITPVASATQSVSRLQSIVAGLKNAPSDQLINIFESCV
  RNPVENIMKILKGIGETFCQHYTQSTDEQPGSHIDFAVNRLKLAEILYYKILETVMVQET
  RRLHGMDMSVLLEQDIFHRSLMACCLEIVLFAYSSPRTFPWIIEVLNLQPFYFYKVIEVV
  IRSEEGLSRDMVKHLNSIEEQILESLAWSHDSALWEALQVSANKVPTCEEVIFPNNFETG
  NGGNVQGHLPLMPMSPLMHPRVKEVRTDSGSLRRDMQPLSPISVHERYSSPTAGSAKRRL
  FGEDPPKEMLMDKIITEGTKLKIAPSSSITAENVSILPGQTLLTMATAPVTGTTGHKVTI
  PLHGVANDAGEITLIPLSMNTNQESKVKSPVSLTAHSLIGASPKQTNLTKAQEVHSTGIN
  RPKRTGSLALFYRKVYHLASVRLRDLCLKLDVSNELRRKIWTCFEFTLVHCPDLMKDRHL
  DQLLLCAFYIMAKVTKEERTFQEIMKSYRNQPQANSHVYRSVLLKSIPREVVAYNKNIND
  DFEMIDCDLEDATKTPDCSSGPVKEERGDLIKFYNTIYVGRVKSFALKYDLANQDHMMDA
  PPLSPFPHIKQQPGSPRRISQQHSIYISPHKNGSGLTPRSALLYKFNGSPSKSLKDINNM
  IRQGEQRTKKRVIAIDSDAESPAKRVCQENDDVLLKRLQDVVSERANH
• Function: Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation. May act as a tumor suppressor.
• KEGG Pathway:
  Cell cycle (hsa04110)
  Cellular senescence (hsa04218)
  TGF-beta sig.ling pathway (hsa04350)
  Human papillomavirus infection (hsa05165)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 (R-HSA-1362300)
  G0 and Early G1 (R-HSA-1538133)
  SMAD2/SMAD3 (R-HSA-2173796)
  TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest (R-HSA-6804114)
  G1/S-Specific Transcription (R-HSA-69205)
  Cyclin D associated events in G1 (R-HSA-69231)
  Transcription of E2F targets under negative control by DREAM complex (R-HSA-1362277)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Genetic Variation	[1]
Prostate cancer	DISF190Y	Definitive	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Definitive	Altered Expression	[2]
Adenoma	DIS78ZEV	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Posttranslational Modification	[6]
Breast carcinoma	DIS2UE88	Strong	Posttranslational Modification	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[8]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[9]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[10]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[10]
Hemangioblastoma	DIS1EAZC	Strong	Biomarker	[11]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[12]
Lung cancer	DISCM4YA	Strong	Altered Expression	[13]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[13]
Neoplasm	DISZKGEW	Strong	Biomarker	[14]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[15]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[11]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[16]
Cervical cancer	DISFSHPF	Limited	Biomarker	[17]
Cervical carcinoma	DIST4S00	Limited	Biomarker	[17]

29 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 Retinoblastoma-like protein 1 (RBL1).	[18]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[19]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Retinoblastoma-like protein 1 (RBL1).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[22]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Retinoblastoma-like protein 1 (RBL1).	[23]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[24]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[27]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[27]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Retinoblastoma-like protein 1 (RBL1).	[28]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Retinoblastoma-like protein 1 (RBL1).	[29]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[30]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[31]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[32]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[33]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[34]
Ritonavir	DMU764S	Approved	Ritonavir increases the expression of Retinoblastoma-like protein 1 (RBL1).	[35]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[36]
Flavopiridol	DMKSUOI	Phase 2	Flavopiridol decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[37]
R-roscovitine	DMSH108	Phase 2	R-roscovitine decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[34]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Retinoblastoma-like protein 1 (RBL1).	[38]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[39]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Retinoblastoma-like protein 1 (RBL1).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[41]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[42]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[34]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Retinoblastoma-like protein 1 (RBL1).	[43]
GW-3965	DMG60ET	Investigative	GW-3965 decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[44]
PD-158780	DMQXYE9	Investigative	PD-158780 decreases the expression of Retinoblastoma-like protein 1 (RBL1).	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the methylation of Retinoblastoma-like protein 1 (RBL1).	[25]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the phosphorylation of Retinoblastoma-like protein 1 (RBL1).	[26]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Retinoblastoma-like protein 1 (RBL1).	[40]

References

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• [41] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [42] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
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