Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0WOOKQ)

• DOT Name: Tumor protein 63 (TP63)
• Synonyms: p63; Chronic ulcerative stomatitis protein; CUSP; Keratinocyte transcription factor KET; Transformation-related protein 63; TP63; Tumor protein p73-like; p73L; p40; p51
• Gene Name: TP63
• Related Disease:
  ADULT syndrome
  Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome
  Cervical cancer
  Congenital deformities of limbs
  Ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3
  Head-neck squamous cell carcinoma
  Limb-mammary syndrome
  Lung neoplasm
  Rapp-Hodgkin syndrome
  Bladder cancer
  Breast disorder
  Breast neoplasm
  Cleft lip
  Cleft lip and alveolus
  Cleft lip/palate
  Colon cancer
  Colorectal neoplasm
  Gastroesophageal reflux disease
  Isolated cleft lip
  Keratitis
  Lymphoma
  Non-alcoholic fatty liver disease
  Pancreatic cancer
  Pancreatic tumour
  Patent ductus arteriosus
  Premature ovarian failure 21
  Prostate carcinoma
  Prostate neoplasm
  Sensorineural hearing loss disorder
  Squamous cell neoplasm
  Sweat gland neoplasm
  Tooth agenesis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Split hand-foot malformation 4
  EEC syndrome
  Split hand-foot malformation
  Breast carcinoma
  Carcinoma
  Colorectal carcinoma
  Isolated cleft palate
  Prostate cancer
  Syndactyly
  Undifferentiated carcinoma
• UniProt ID: P63_HUMAN
• PDB ID: 1RG6; 2NB1; 2RMN; 2Y9T; 2Y9U; 3QYM; 3QYN; 3US0; 3US1; 3US2; 3ZY0; 3ZY1; 4A9Z; 6FGN; 6RU6; 6RU7; 6RU8; 7Z71; 7Z72; 7Z73; 7Z7E; 8P9C; 8P9D; 8P9E
• Pfam ID: PF00870 ; PF07710 ; PF07647
• Sequence:
  MNFETSRCATLQYCPDPYIQRFVETPAHFSWKESYYRSTMSQSTQTNEFLSPEVFQHIWD
  FLEQPICSVQPIDLNFVDEPSEDGATNKIEISMDCIRMQDSDLSDPMWPQYTNLGLLNSM
  DQQIQNGSSSTSPYNTDHAQNSVTAPSPYAQPSSTFDALSPSPAIPSNTDYPGPHSFDVS
  FQQSSTAKSATWTYSTELKKLYCQIAKTCPIQIKVMTPPPQGAVIRAMPVYKKAEHVTEV
  VKRCPNHELSREFNEGQIAPPSHLIRVEGNSHAQYVEDPITGRQSVLVPYEPPQVGTEFT
  TVLYNFMCNSSCVGGMNRRPILIIVTLETRDGQVLGRRCFEARICACPGRDRKADEDSIR
  KQQVSDSTKNGDGTKRPFRQNTHGIQMTSIKKRRSPDDELLYLPVRGRETYEMLLKIKES
  LELMQYLPQHTIETYRQQQQQQHQHLLQKQTSIQSPSSYGNSSPPLNKMNSMNKLPSVSQ
  LINPQQRNALTPTTIPDGMGANIPMMGTHMPMAGDMNGLSPTQALPPPLSMPSTSHCTPP
  PPYPTDCSIVSFLARLGCSSCLDYFTTQGLTTIYQIEHYSMDDLASLKIPEQFRHAIWKG
  ILDHRQLHEFSSPSHLLRTPSSASTVSVGSSETRGERVIDAVRFTLRQTISFPPRDEWND
  FNFDMDARRNKQQRIKEEGE
• Function: Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.
• Tissue Specificity: Widely expressed, notably in heart, kidney, placenta, prostate, skeletal muscle, testis and thymus, although the precise isoform varies according to tissue type. Progenitor cell layers of skin, breast, eye and prostate express high levels of DeltaN-type isoforms. Isoform 10 is predominantly expressed in skin squamous cell carcinomas, but not in normal skin tissues.
• KEGG Pathway: MicroR.s in cancer (hsa05206)
• Reactome Pathway:
  Pyroptosis (R-HSA-5620971)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
  TP53 Regulates Transcription of Genes Involved in Cytochrome C Release (R-HSA-6803204)
  TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain (R-HSA-6803205)
  TP53 Regulates Transcription of Caspase Activators and Caspases (R-HSA-6803207)
  TP53 Regulates Transcription of Death Receptors and Ligands (R-HSA-6803211)
  Regulation of TP53 Activity through Association with Co-factors (R-HSA-6804759)
  Activation of PUMA and translocation to mitochondria (R-HSA-139915)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
ADULT syndrome	DISIXF16	Definitive	Autosomal dominant	[1]
Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome	DISRVSZF	Definitive	Autosomal dominant	[2]
Cervical cancer	DISFSHPF	Definitive	Biomarker	[3]
Congenital deformities of limbs	DISP4N1Q	Definitive	Genetic Variation	[4]
Ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3	DISGAIXY	Definitive	Autosomal dominant	[1]
Head-neck squamous cell carcinoma	DISF7P24	Definitive	Biomarker	[5]
Limb-mammary syndrome	DIS7H4FP	Definitive	Autosomal dominant	[6]
Lung neoplasm	DISVARNB	Definitive	Biomarker	[7]
Rapp-Hodgkin syndrome	DISCNGW9	Definitive	Autosomal dominant	[2]
Bladder cancer	DISUHNM0	Strong	Biomarker	[8]
Breast disorder	DISJTGMA	Strong	Biomarker	[9]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[10]
Cleft lip	DISV3XW6	Strong	CausalMutation	[11]
Cleft lip and alveolus	DISD651B	Strong	SusceptibilityMutation	[12]
Cleft lip/palate	DIS14IG3	Strong	Genetic Variation	[13]
Colon cancer	DISVC52G	Strong	Biomarker	[14]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[15]
Gastroesophageal reflux disease	DISQ8G5S	Strong	Biomarker	[16]
Isolated cleft lip	DIS2O2JV	Strong	Genetic Variation	[17]
Keratitis	DISMFOEI	Strong	Genetic Variation	[18]
Lymphoma	DISN6V4S	Strong	Altered Expression	[19]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Genetic Variation	[20]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[21]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[22]
Patent ductus arteriosus	DIS9P8YS	Strong	Biomarker	[23]
Premature ovarian failure 21	DISN1FHW	Strong	Autosomal dominant	[24]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[25]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[26]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Genetic Variation	[27]
Squamous cell neoplasm	DISKBRLI	Strong	Biomarker	[28]
Sweat gland neoplasm	DISQ2Y02	Strong	Biomarker	[29]
Tooth agenesis	DIS1PWC7	Strong	Genetic Variation	[30]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[31]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[31]
Split hand-foot malformation 4	DISII2HN	Moderate	Autosomal dominant	[32]
EEC syndrome	DISIYS7L	Supportive	Autosomal dominant	[33]
Split hand-foot malformation	DIS8PKGD	Supportive	Autosomal dominant	[2]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[34]
Carcinoma	DISH9F1N	Limited	Biomarker	[35]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[36]
Isolated cleft palate	DISV80CD	Limited	Altered Expression	[37]
Prostate cancer	DISF190Y	Limited	Biomarker	[25]
Syndactyly	DISZK2BT	Limited	Genetic Variation	[38]
Undifferentiated carcinoma	DISIAZST	Limited	Biomarker	[39]

37 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 Tumor protein 63 (TP63).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tumor protein 63 (TP63).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tumor protein 63 (TP63).	[42]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tumor protein 63 (TP63).	[43]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Tumor protein 63 (TP63).	[44]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tumor protein 63 (TP63).	[45]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Tumor protein 63 (TP63).	[46]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Tumor protein 63 (TP63).	[47]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Tumor protein 63 (TP63).	[49]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Tumor protein 63 (TP63).	[50]
Topotecan	DMP6G8T	Approved	Topotecan decreases the expression of Tumor protein 63 (TP63).	[51]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Tumor protein 63 (TP63).	[52]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tumor protein 63 (TP63).	[53]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Tumor protein 63 (TP63).	[47]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Tumor protein 63 (TP63).	[54]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin decreases the expression of Tumor protein 63 (TP63).	[51]
OSI-906	DMHKZLF	Phase 3	OSI-906 decreases the expression of Tumor protein 63 (TP63).	[55]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Tumor protein 63 (TP63).	[56]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Tumor protein 63 (TP63).	[57]
Eugenol	DM7US1H	Patented	Eugenol decreases the expression of Tumor protein 63 (TP63).	[59]
Flavonoid derivative 1	DMCQP0B	Patented	Flavonoid derivative 1 increases the expression of Tumor protein 63 (TP63).	[44]
PD-153035	DM7KJTI	Discontinued in Phase 1	PD-153035 decreases the expression of Tumor protein 63 (TP63).	[49]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Tumor protein 63 (TP63).	[60]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tumor protein 63 (TP63).	[61]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Tumor protein 63 (TP63).	[62]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Tumor protein 63 (TP63).	[63]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Tumor protein 63 (TP63).	[64]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Tumor protein 63 (TP63).	[65]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal increases the expression of Tumor protein 63 (TP63).	[66]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Tumor protein 63 (TP63).	[67]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Tumor protein 63 (TP63).	[68]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the expression of Tumor protein 63 (TP63).	[69]
Chrysin	DM7V2LG	Investigative	Chrysin increases the expression of Tumor protein 63 (TP63).	[44]
Kaempferol	DMHEMUB	Investigative	Kaempferol increases the expression of Tumor protein 63 (TP63).	[44]
Apigenin	DMI3491	Investigative	Apigenin increases the expression of Tumor protein 63 (TP63).	[70]
Myricetin	DMTV4L0	Investigative	Myricetin increases the expression of Tumor protein 63 (TP63).	[70]
4-[1-(4-hydroxyphenyl)-2-phenylbut-1-enyl]phenol	DMTMLXU	Investigative	4-[1-(4-hydroxyphenyl)-2-phenylbut-1-enyl]phenol increases the expression of Tumor protein 63 (TP63).	[57]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Tumor protein 63 (TP63).	[48]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Tumor protein 63 (TP63).	[58]

References

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