Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Video

Updated: May 21, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
05:17

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay

Published on: February 9, 2021

P53 mdm2 inhibitors.

Kareem Khoury1, Alex Dömling

  • 1University of Pittsburgh, Department of Pharmaceutical Sciences, Pittsburgh, PA 15261, USA.

Current Pharmaceutical Design
|June 2, 2012
PubMed
Summary
This summary is machine-generated.

Small molecules inhibiting the p53-MDM2 interaction are crucial for cancer prevention. This review details small molecules that bind MDM2, offering structural insights and synthetic routes for potential cancer therapies.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

1,4,5-Trisubstituted Imidazole-Based p53-MDM2/MDMX Antagonists with Aliphatic Linkers for Conjugation with Biological Carriers.

Journal of medicinal chemistry·2017
Same author

Concise Synthesis of Tetrazole-keto-piperazines by Two Consecutive Ugi Reactions.

European journal of organic chemistry·2016
Same author

Leuckart-Wallach Route Toward Isocyanides and Some Applications.

ACS combinatorial science·2015
Same author

MCR synthesis of a tetracyclic tetrazole scaffold.

Bioorganic & medicinal chemistry·2015
Same author

A universal isocyanide for diverse heterocycle syntheses.

Organic letters·2014
Same author

The p53-MDM2/MDMX axis - A chemotype perspective.

MedChemComm·2014

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Medicinal Chemistry

Background:

  • The p53-MDM2 protein-protein interaction (PPI) is a critical regulator in cancer prevention.
  • This interaction is conformation-based and tightly regulated.
  • Understanding structural requirements for MDM2 inhibitors is key to developing cancer therapies.

Purpose of the Study:

  • To review small molecules that inhibit the p53-MDM2 interaction.
  • To summarize binding characteristics of disclosed inhibitors with co-crystal structures.
  • To detail synthetic access and derivatives of these inhibitory compounds.

Main Methods:

  • Structural analysis of MDM2-inhibitor complexes.
  • Review of published co-crystal structures.

More Related Videos

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

Related Experiment Videos

Last Updated: May 21, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
05:17

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay

Published on: February 9, 2021

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Purification of Ubiquitinated p53 Proteins from Mammalian Cells
10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

  • Summary of synthetic chemistry approaches.

    • Main Results:

    • Detailed characterization of small molecules binding to MDM2.
    • Provided Angstrom-level structural insights into inhibitor binding.
    • Described synthetic pathways for disclosed inhibitors and their analogs.

    Conclusions:

    • Small molecule inhibitors targeting the p53-MDM2 interaction are viable for cancer therapy development.
    • Co-crystal structures provide valuable information for rational drug design.
    • Synthetic accessibility of these inhibitors facilitates further research and development.