Reactivation Of Mutant p53 With A New Classes Of Small Molecules
- 技术优势
- • Effective binding to mutant p53 • Ability to induce cell death in cells with mutant p53
- 详细技术说明
- A novel class of small molecules that can reactivate mutant p53 leading to apoptosis in cancer cells.#therapeutics #cancer
- *Abstract
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Northwestern researchers have identified a new class of small molecules that are capable of inducing apoptosis by reactivating mutant p53 in transformed cells. These novel compounds induce apoptosis in cancer cells by promoting mutant p53 binding to target DNA and thus reactivating the ability of p53 to act as a tumor suppressor. These compounds are designed based on the structure of PRIMA-1 which is a molecule demonstrated to effectively bind to mutant p53. The investigators have already demonstrated that these novel compounds and their derivatives are able to induce cell death in cells containing mutant p53. In healthy cells, p53 controls the integrity of cellular DNA by arresting cell proliferation, initiating cell death or mediating DNA repair in the event of DNA damage. Thus, by inducing cell death, p53 acts as a tumor suppressor by preventing a cell with damaged DNA from dividing. Many chemotherapeutic approaches aim to damage DNA and induce activation of the p53 protein and its ability to induce cellular apoptosis. However, if p53 function is blocked, such chemotherapeutic approaches are not effective, as p53 is unable to activate the apoptotic cascade. Mutations in p53 are the most common genetic abnormalities shown to be associated with human cancer. About 60% of human cancers, including lung, stomach, breast, colon, liver, prostate, head and neck, esophageal, leukemia, lymphoma, ovary and bladder, exhibit defects in the gene as point mutations, deletions or insertions.
- *Inventors
- Daniel H. Appella Michael C. Myers Gerard Zambetti Toshiaki Hara
- 国家/地区
- 美国
