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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
p53 as a potential target for treatment of cancer: A perspective on recent advancements in small molecules with
Chahat1, Rohit Bhatia1, Bhupinder Kumar2
1Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Ghal Kalan, Ferozpur G.T. Road MOGA, 142001, Punjab, India.
Abstract:
Cancer represents one of the world's biggest hazardous diseases. p53 is the uttermost researched tumour suppressor protein. It is commonly considered the "guardian of the genome," performing a critical function in genetic stability maintenance through controlling the cell cycle, programmed cell death, DNA repair, aging, and angiogenesis. The abnormalities in p53 lead to genetic instability and plays a significant role in carcinogenesis. The role of p53 in tumour suppression is emphasized in addition by the observation that primary silencing with this protein occurred in more than 50% of cancers. MDM2, p53, and the p53-MDM2 connections are well-known targets for the prevention and treatment of cancer. Moreover, in tumors with wild-type p53, their efficacy is decreased due to MDM2 enlargement or by the gradual decrease of MDM2 blocker ARF. As a result, improving p53 activity in cancerous cells provides a promising anticancer strategy. Various techniques are now being investigated, and addressing the p53-MDM2 interaction had also evolved as a potentially feasible strategy for contending with tumors. Both p53 and MDM2, interact via an autoregulation response signal: p53 activity induces MDM2 transcription, which in response interacts with p53's N-terminal transactivation domain, inhibiting its transcriptional activity. This article provides information on the current scenario of anti-tumor activities, with a particular emphasis on structure-activity relationship characteristics (SAR) against the p53-MDM2 to treat cancer. The primary purpose of this review is to cover recent advancements in the creation and testing of anticancer drugs that target the p53-MDM2 structure. This review contains different heterocyclic moieties which show significant results toward cancer. A mechanistic route is shown here, demonstrating both normal and malignant conditions via several stressed factors. Several compounds entered clinical trials as p53-MDM2 inhibitors for the treatment of cancer.
Insights
Targeting the p53-MDM2 interaction is a promising anticancer strategy. This review highlights structure-activity relationships of novel inhibitors for cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Medicinal Chemistry
Background:
- Cancer is a leading global health threat.
- The p53 protein, or "guardian of the genome," is crucial for genetic stability and tumor suppression.
- p53 dysfunction is implicated in over 50% of cancers, making it a key therapeutic target.
Purpose of the Study:
- To review current anti-cancer strategies targeting the p53-MDM2 interaction.
- To emphasize structure-activity relationship (SAR) characteristics of p53-MDM2 inhibitors.
- To cover recent advancements in the development and testing of novel anticancer drugs.
Main Methods:
- Review of literature on p53-MDM2 interaction inhibitors.
- Analysis of structure-activity relationships (SAR) for anti-cancer drug development.
- Exploration of heterocyclic moieties with anti-cancer properties.
Main Results:
- The p53-MDM2 autoregulation loop is a critical target for cancer therapy.
- Inhibiting the p53-MDM2 interaction shows promise for treating tumors, especially those with wild-type p53.
- Several novel compounds targeting this interaction have entered clinical trials.
Conclusions:
- Enhancing p53 activity by targeting the p53-MDM2 interaction is a viable anti-cancer strategy.
- Structure-activity relationship studies are vital for designing effective p53-MDM2 inhibitors.
- Continued research into heterocyclic compounds offers potential for new cancer therapeutics.
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