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Mouse double minute 2 homolog (MDM2) also known as E3 ubiquitin-protein ligase Mdm2 is a protein that in humans is encoded by the MDM2 gene. Mdm2 is an important negative regulator of the p53 tumor suppressor. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain (TAD) of the p53 tumor suppressor and as an inhibitor of p53 transcriptional
Link: https://en.wikipedia.org/wiki/Mdm2 (Actived: Thursday Jun 20, 2019)
The three major biomarkers that have been used to evaluate therapeutic responses to MDM2/X inhibitors are p53 status, MDM2, and MDMX levels. Interestingly, the over expression of MDM2, MDMX, or mutation of p53 are often mutually exclusive.
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728205/ (Actived: Saturday Jan 15, 2011)
Resistance to treatment occurs through the development of P53 mutant-clones and as result of other molecular defects and/or altered expression of molecules, such as MDMX, that can confer resistance to MDM2 inhibitors. Hoffman-Luca and colleagues have recently addressed the mechanisms of acquired resistance focusing on the MDM2 inhibitor SAR405838.
Link: https://jhoonline.biomedcentral.com/articles/10.1186/s13045-017-0500-5 (Actived: Tuesday Jun 18, 2019)
Design of small-molecule inhibitors (MDM2 inhibitors) to block the MDM2–p53 protein–protein interaction has been pursued as a new cancer therapeutic strategy. In recent years, potent, selective, and efficacious MDM2 inhibitors have been successfully obtained and seven such compounds have been advanced into early phase clinical trials for the treatment of human cancers.
Link: http://pubs.acs.org/doi/abs/10.1021/jm501092z (Actived: Sunday Apr 7, 2019)
MDM2 inhibitor AMG-232 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving MDM2 inhibitor AMG-232 and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Link: https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/mdm2-inhibitor-amg-232 (Actived: Thursday Jun 20, 2019)
MX69 is a MDM2/XIAP inhibitor that binds to MDM2 RING protein with binding Kd values of 2.34 μM. It is used for cancer treatment. S8606: HDM201. HDM201 is a novel, highly potent and selective inhibitor of the p53-Mdm2 interaction with affinity constant for Mdm2 in the picomolar range and a selectivity ratio greater than 10000-fold vs Mdm4.
Link: https://www.selleckchem.com/mdm2.html (Actived: Friday Jun 14, 2019)
Inhibitors of the p53–MDM2 interaction activate p53 by direct interference with MDM2 binding and thus can fully compensate for any defects in the upstream components of the p53 pathway. However, defective downstream p53 signaling might substantially decrease their effectiveness.
Link: https://www.sciencedirect.com/science/article/pii/S1471491406002590 (Actived: Wednesday May 29, 2019)
3. NUTLIN. Hoffmann La Roche set out via high throughput screening to find potent and selective p53/MDM2 inhibitors. One class of compounds was a series of cis-imidazoline analogs termed Nutlins (Scheme 1).These compounds displaced p53 from MDM2 with an IC50 in the 100 to 300 nM range.
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719986/ (Actived: Thursday Feb 17, 2005)
Link: https://www.scbt.com/scbt/browse/MDM2-Inhibitors/_/N-f7ukod (Actived: Thursday Jun 6, 2019)
Link: https://medicalxpress.com/news/2018-11-mdm2-inhibitors-treatment-uveitis.html (Actived: Wednesday Oct 31, 2018)
MDM2 Inhibitor is a cell-permeable boranyl-chalcone exhibiting strong binding to MDM2 and irreversibly disrupts the MDM2/p53 protein complex. A10657 SALE: Nutlin-3: Mdm2 antagonist : MDM2 antagonist nutlin-3 is a potent inducer of apoptosis. Product Citations (4)
Link: https://www.adooq.com/mdm2.html (Actived: Wednesday Jun 12, 2019)