Star tumor suppressor gene p53


Introduction

P53 tumor suppressor gene is a kind of gene that inhibits cells from transforming into cancer cells in living organisms. There are oncogene and tumor suppressor gene in the cell already, and so long as one side produces the pathological change and loses the balance, cancer may occur. Human p53 gene, located on chromosome 17 p13, is a nuclear-phosphorylated protein with a full length of 16-20kb and 11 exons. The mRNA, encoding 2.8kb is a p53 protein. Up to now, p53 is the most associated gene with the human tumor. It used to be regarded as an oncogene, until 1989, when the role of oncogene was known to be a mutated p53, and it was later confirmed that wild-type p53 is a tumor suppressor gene. P53 protein, a product of p53 gene expression, is composed of 393 amino acid residues and exists as a tetramer in vivo. The half-life of p53 protein is 20-30 minutes.

The Mechanism of P53

Under normal circumstances, the content of p53 protein in cells is very low, because its half-life is short, so it is difficult to detect, but in the growth of value-added cells, can be increased more than 5-100 times. Wild-type p53 protein plays an important role in maintaining the normal growth of cells and inhibiting malignant proliferation, so it is called “gene guardian”. P53 gene constantly monitors the integrity of the cell chromosome DNA. Once the cell chromosome DNA is damaged, p53 protein binds to the corresponding binding site of the gene DNA, acts as a special transcription factor, and activates the transcription of p21 gene. The cells were arrested in G1 phase and inhibit the activity of lyase and interacts with replicator A to participate in the replication and repair of DNA. If the repair fails, the p53 protein starts the process of programmed death (apoptosis) to induce cell suicide, prevent the generation of cancer-prone mutant cells, therefore preventing the malignant transformation of cells.

When p53 gene mutates, because the spatial conformation affects the function of transcription activation and the phosphorylation process of p53 protein, it not only loses the function of wild-type p53 in inhibiting tumor proliferation but also makes the gene possess the function of the oncogene. The mutant p53 protein binds to the wild-type p53 protein, and the resulting widowhood protein fails to bind to DNA, causing the transcription of some cancer-related genes to get out of control and lead to tumorigenesis.

Phase Code Name (CD) Generic Name (GN) Organization Condition
Preclinical PFTalpha Pifithrin-alpha Quark Pharmaceuticals; University of Illinois (Originator); Stroke; Dementia, Alzheimer’s type; Parkinson’s disease; Cancer
Preclinical Nutlin-3 Roche (Originator); Cancer
Preclinical (-)-Nutlin-3; Nutlin-3-(-); Nutlin-3-enantiomer A; Nutlin-3A Roche (Originator); Cancer, solid tumor; Cancer
Preclinical Tenovin-1 Institute of Molecular and Cell Biology (Originator); University of Dundee (Originator); University of St. Andrews (Originator); Cancer
Preclinical DIMP-53-1 Universidade do Porto (Originator); Universidade de Lisboa (Originator); Cancer
Preclinical HZT-703 Aspirin/famotidine Horizon Pharma (Originator); Pain
Preclinical P-1539 Piramal Phytocare (Originator); Inflammation
Preclinical CVM-01; NONO-ASA University of Alberta (Originator); Pain; Inflammation; Fever; Ulcer, peptic
Preclinical TAC/p53 Wuhan University (Originator); Cancer
Preclinical CER-628 Cerenis Therapeutics (Originator); Lipoprotein disorders
Preclinical Dimethyl fumarate/acetylsalicylic acid Vitalis (Originator); Multiple sclerosis
Phase I CBL-0137; CBLC-137; CX-137 Cleveland Biolabs (Originator); Incuron; Neuroblastoma; Lymphoma; Cancer, solid tumor; Trypanosomiasis
Phase I CGM-097; NVP-CGM-097 Novartis (Originator); Cancer, solid tumor
Phase I CBL-0137; CBLC-137; CX-137 Cleveland Biolabs (Originator); Incuron; Neuroblastoma; Lymphoma; Cancer, solid tumor; Trypanosomiasis
Phase I PA-65020 Acetylsalicylic acid/omeprazole Aralez Pharmaceuticals (Originator); Pain
Phase I Acetylsalicylic acid/pantoprazole sodium GlaxoSmithKline (Originator); Ulcer, peptic
Phase I Aspirin/TAK-438; TAK-438-ASA; TAK-438ASA Takeda (Originator); Unidentified condition
Phase II Thioureidobutyronitrile hydrochloride Innovation Pharmaceuticals (Originator); Formatech; Cancer, kidney; Cancer, pancreas; Leukemia, acute myeloid; Multiple myeloma; Lymphoma; Cancer, solid tumor; Cancer, ovary; Glioma; Retinoblastoma; Cancer
Phase II Thioureidobutyronitrile hydrochloride Innovation Pharmaceuticals (Originator); Formatech; Cancer, kidney; Cancer, pancreas; Leukemia, acute myeloid; Multiple myeloma; Lymphoma; Cancer, solid tumor; Cancer, ovary; Glioma; Retinoblastoma; Cancer
Phase II CER-627 Niacin/aspirin Cerenis Therapeutics (Originator); Lipoprotein disorders
Phase II VVD-101 Acetylsalicylic acid/sumatriptan succinate Vivid Pharma; Headache
Phase III Aspirin/simvastatin/lisinopril/
hydrochlorothiazide
Dr Reddy’s Laboratories (Originator); Other cardiovascular disorders
Phase III I5NP; QPI-1002; AKIi-5 (former code); DGFi (former code) Silence Therapeutics (Originator); Quark Pharmaceuticals; Alnylam Pharmaceuticals; Delayed Graft Function; Acute kidney injury