Target General Infomation
Target ID
T15739 (Former ID: TTDC00118)
Target Name
Cellular tumor antigen p53 (TP53)
Synonyms
Tumor suppressor p53; Phosphoprotein p53; P53; Antigen NY-CO-13
Gene Name
TP53
Target Type
Clinical trial target
[1]
Disease [+] 2 Target-related Diseases +
1 Lip/oral cavity/pharynx neoplasm [ICD-11: 2B6E]
2 Transplant rejection [ICD-11: NE84]
Function
Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2. Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type.
UniProt ID
P53_HUMAN
Sequence
MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGP
DEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAK
SVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRRCPHHE
RCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNS
SCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHELP
PGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEPG
GSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDSD
Drugs and Modes of Action
Clinical Trial Drug(s) [+] 16 Clinical Trial Drugs +
1 Contusugene ladenovec Drug Info Phase 3 Oral cancer [2]
2 QPI-1002 Drug Info Phase 3 Renal transplantation [3]
3 ALT-801 Drug Info Phase 2 Acute myeloid leukaemia [4]
4 APR-246 Drug Info Phase 2 Ovarian cancer [5]
5 INGN-225 Drug Info Phase 2 Head and neck cancer [6]
6 Kevetrin Drug Info Phase 2 Ovarian cancer [5]
7 SGT-53 Drug Info Phase 2 Pancreatic cancer [5]
8 ISA-P53-01 Drug Info Phase 1/2 Colorectal cancer [7]
9 APG-115 Drug Info Phase 1 Lymphoma [5]
10 CGM097 Drug Info Phase 1 Solid tumour/cancer [8]
11 COTI-2 Drug Info Phase 1 Cervical cancer [5]
12 Dendritic cell vaccine Drug Info Phase 1 Head and neck cancer [9]
13 HDM201 Drug Info Phase 1 Haematological malignancy [10]
14 ONYX-015 Drug Info Phase 1 Head and neck cancer [11]
15 SAR-405838 Drug Info Phase 1 Solid tumour/cancer [12]
16 Thioureidobutyronitrile Drug Info Phase 1 Solid tumour/cancer [13]
Discontinued Drug(s) [+] 4 Discontinued Drugs +
1 INGN-234 Drug Info Discontinued in Phase 2 Oral cancer [14]
2 Ad-p53 Drug Info Discontinued in Phase 1 Solid tumour/cancer [15]
3 Pifithrin-alpha Drug Info Terminated Toxicity [16]
4 TAR-1 Drug Info Terminated Solid tumour/cancer [17]
Mode of Action [+] 5 Modes of Action +
Modulator [+] 9 Modulator drugs +
1 Contusugene ladenovec Drug Info [1]
2 QPI-1002 Drug Info [18]
3 CGM097 Drug Info [18]
4 COTI-2 Drug Info [5]
5 ONYX-015 Drug Info [24], [25]
6 SAR-405838 Drug Info [26], [27]
7 Thioureidobutyronitrile Drug Info [29]
8 Ad-p53 Drug Info [31]
9 ALT-801 (bolus injection), Altor Drug Info [4]
Immunomodulator (Immunostimulant) [+] 1 Immunomodulator (Immunostimulant) drugs +
1 ALT-801 Drug Info [4]
Stimulator [+] 3 Stimulator drugs +
1 Kevetrin Drug Info [5]
2 APR-246 Drug Info [21]
3 SGT-53 Drug Info [28]
Inhibitor [+] 6 Inhibitor drugs +
1 APG-115 Drug Info [5]
2 HDM201 Drug Info [23]
3 Pifithrin-alpha Drug Info [32]
4 1-(9-ethyl-9H-carbazol-3-yl)-N-methylmethanamine Drug Info [34]
5 NU-8231 Drug Info [35]
6 NUTLIN-3 Drug Info [36]
Suppressor [+] 1 Suppressor drugs +
1 INGN-234 Drug Info [30]
Target Regulators
Target-regulating microRNAs
Target-regulating Transcription Factors
Target-interacting Proteins
Target Profiles in Patients
Target Expression
 Profile (TEP)
Drug Resistance
 Mutation (DRM)
Target Affiliated Biological Pathways
KEGG Pathway [+] 35 KEGG Pathways +
1 MAPK signaling pathway
2 Sphingolipid signaling pathway
3 Cell cycle
4 p53 signaling pathway
5 PI3K-Akt signaling pathway
6 Apoptosis
7 Wnt signaling pathway
8 Neurotrophin signaling pathway
9 Thyroid hormone signaling pathway
10 Amyotrophic lateral sclerosis (ALS)
11 Huntington's disease
12 Hepatitis C
13 Hepatitis B
14 Measles
15 HTLV-I infection
16 Herpes simplex infection
17 Epstein-Barr virus infection
18 Pathways in cancer
19 Transcriptional misregulation in cancer
20 Viral carcinogenesis
21 Proteoglycans in cancer
22 MicroRNAs in cancer
23 Colorectal cancer
24 Pancreatic cancer
25 Endometrial cancer
26 Glioma
27 Prostate cancer
28 Thyroid cancer
29 Basal cell carcinoma
30 Melanoma
31 Bladder cancer
32 Chronic myeloid leukemia
33 Small cell lung cancer
34 Non-small cell lung cancer
35 Central carbon metabolism in cancer
NetPath Pathway [+] 1 NetPath Pathways +
1 FSH Signaling Pathway
Panther Pathway [+] 7 Panther Pathways +
1 Apoptosis signaling pathway
2 Huntington disease
3 Wnt signaling pathway
4 p53 pathway
5 P53 pathway feedback loops 1
6 p53 pathway by glucose deprivation
7 p53 pathway feedback loops 2
PID Pathway [+] 13 PID Pathways +
1 Signaling events mediated by HDAC Class III
2 Validated targets of C-MYC transcriptional activation
3 LKB1 signaling events
4 Glucocorticoid receptor regulatory network
5 Direct p53 effectors
6 p75(NTR)-mediated signaling
7 AP-1 transcription factor network
8 Hypoxic and oxygen homeostasis regulation of HIF-1-alpha
9 Signaling mediated by p38-alpha and p38-beta
10 Aurora A signaling
11 BARD1 signaling events
12 p53 pathway
13 PLK3 signaling events
Reactome [+] 12 Reactome Pathways +
1 Activation of NOXA and translocation to mitochondria
2 Activation of PUMA and translocation to mitochondria
3 Pre-NOTCH Transcription and Translation
4 Oxidative Stress Induced Senescence
5 Formation of Senescence-Associated Heterochromatin Foci (SAHF)
6 Oncogene Induced Senescence
7 DNA Damage/Telomere Stress Induced Senescence
8 Autodegradation of the E3 ubiquitin ligase COP1
9 TP53 Regulates Metabolic Genes
10 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
11 Stabilization of p53
12 Factors involved in megakaryocyte development and platelet production
WikiPathways [+] 38 WikiPathways +
1 DNA Damage Response (only ATM dependent)
2 DNA Damage Response
3 ErbB Signaling Pathway
4 Senescence and Autophagy in Cancer
5 G1 to S cell cycle control
6 Sandbox Pathway
7 Wnt Signaling Pathway and Pluripotency
8 MAPK Signaling Pathway
9 TGF beta Signaling Pathway
10 Copper homeostasis
11 Bladder Cancer
12 Mammary gland development pathway - Involution (Stage 4 of 4)
13 Pre-NOTCH Expression and Processing
14 Apoptosis
15 ATM Signaling Pathway
16 Amyotrophic lateral sclerosis (ALS)
17 Retinoblastoma (RB) in Cancer
18 Spinal Cord Injury
19 Integrated Pancreatic Cancer Pathway
20 Oncostatin M Signaling Pathway
21 Gastric cancer network 2
22 Prostate Cancer
23 Signaling Pathways in Glioblastoma
24 Metastatic brain tumor
25 Alzheimers Disease
26 Integrated Breast Cancer Pathway
27 Integrated Cancer pathway
28 Intrinsic Pathway for Apoptosis
29 Factors involved in megakaryocyte development and platelet production
30 Cell Cycle
31 Cell Cycle Checkpoints
32 Apoptosis Modulation and Signaling
33 Folate Metabolism
34 TP53 Network
35 Fluoropyrimidine Activity
36 miRNAs involved in DNA damage response
37 miRNA Regulation of DNA Damage Response
38 AMPK Signaling
Target-Related Models and Studies
Target Validation
References
REF 1 A review of contusugene ladenovec (Advexin) p53 therapy. Curr Opin Mol Ther. 2009 Feb;11(1):54-61.
REF 2 ClinicalTrials.gov (NCT00041613) Study to Compare the Overall Survival of Patients Receiving INGN 201 (Study Drug) With Patients Receiving Methotrexate. U.S. National Institutes of Health.
REF 3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 4 Phase I trial of ALT-801, an interleukin-2/T-cell receptor fusion protein targeting p53 (aa264-272)/HLA-A*0201 complex, in patients with advanced malignancies. Clin Cancer Res. 2011 Dec 15;17(24):7765-75.
REF 5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 6 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019096)
REF 7 Clinical pipeline report, company report or official report of ISA Pharmaceuticals BV.
REF 8 ClinicalTrials.gov (NCT01760525) A Phase I Dose Escalation Study of CGM097 in Adult Patients With Selected Advanced Solid Tumors. U.S. National Institutes of Health.
REF 9 ClinicalTrials.gov (NCT00404339) Vaccine Therapy in Treating Patients With Head and Neck Cancer. U.S. National Institutes of Health.
REF 10 ClinicalTrials.gov (NCT02143635) Study to Determine and Evaluate a Safe and Tolerated Dose of HDM201 in Patients With Selected Advanced Tumors That Are TP53wt. U.S. National Institutes of Health.
REF 11 ClinicalTrials.gov (NCT00006106) ONYX-015 With Cisplatin and Fluorouracil in Treating Patients With Advanced Head and Neck Cancer. U.S. National Institutes of Health.
REF 12 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800036509)
REF 13 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028294)
REF 14 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028790)
REF 15 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004882)
REF 16 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012866)
REF 17 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031168)
REF 18 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
REF 19 INGN-225: a dendritic cell-based p53 vaccine (Ad.p53-DC) in small cell lung cancer: observed association between immune response and enhanced chemotherapy effect. Expert Opin Biol Ther. 2010 Jun;10(6):983-91.
REF 20 WO patent application no. 2013,1850,32, Nanotherapeutics for drug targeting.
REF 21 APR-246/PRIMA-1MET inhibits thioredoxin reductase 1 and converts the enzyme to a dedicated NADPH oxidase. Cell Death Dis. 2013 Oct 24;4:e881.
REF 22 Vaccination with p53-peptide-pulsed dendritic cells, of patients with advanced breast cancer: report from a phase I study. Cancer Immunol Immunother. 2004 Jul;53(7):633-41.
REF 23 National Cancer Institute Drug Dictionary (drug id 761551).
REF 24 Late viral RNA export, rather than p53 inactivation, determines ONYX-015 tumor selectivity. Cancer Cell. 2004 Dec;6(6):611-23.
REF 25 Selective replication and oncolysis in p53 mutant tumors with ONYX-015, an E1B-55kD gene-deleted adenovirus, in patients with advanced head and neck cancer: a phase II trial. Cancer Res. 2000 Nov 15;60(22):6359-66.
REF 26 SAR405838: an optimized inhibitor of MDM2-p53 interaction that induces complete and durable tumor regression. Cancer Res. 2014 Oct 15;74(20):5855-65.
REF 27 SAR405838: A Novel and Potent Inhibitor of the MDM2:p53 Axis for the Treatment of Dedifferentiated Liposarcoma.Clin Cancer Res.2016 Mar 1;22(5):1150-60.
REF 28 Transferrin receptor targeting nanomedicine delivering wild-type p53 gene sensitizes pancreatic cancer to gemcitabine therapy. Cancer Gene Ther. 2013 Apr;20(4):222-8.
REF 29 J Clin Oncol 31, 2013 (suppl; abstr TPS2627).
REF 30 Prevent Oral Cancer With Mouthwash. Introgen Therapeutics.
REF 31 Assessment of p53 gene transfer and biological activities in a clinical study of adenovirus-p53 gene therapy for recurrent ovarian cancer. Cancer Gene Ther. 2003 Mar;10(3):224-38.
REF 32 An evaluation of the ability of pifithrin-alpha and -beta to inhibit p53 function in two wild-type p53 human tumor cell lines. Mol Cancer Ther. 2005 Sep;4(9):1369-77.
REF 33 Regulation of host gene expression by HIV-1 TAR microRNAs. Retrovirology. 2013; 10: 86.
REF 34 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
REF 35 Small-molecule inhibitors of the MDM2-p53 protein-protein interaction based on an isoindolinone scaffold. J Med Chem. 2006 Oct 19;49(21):6209-21.
REF 36 Discovery and optimization of chromenotriazolopyrimidines as potent inhibitors of the mouse double minute 2-tumor protein 53 protein-protein intera... J Med Chem. 2009 Nov 26;52(22):7044-53.

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