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The development of piperidinones as potent MDM2-P53 protein-protein interaction inhibitors for cancer therapy.

A new interesting article has been published in Eur J Med Chem. 2018 Nov 5;159:1-9. doi: 10.1016/j.ejmech.2018.09.044. Epub 2018 Sep 18. Review and titled:

The development of piperidinones as potent MDM2-P53 protein-protein interaction inhibitors for cancer therapy.

Authors of this article are:

Liao G, Yang D, Ma L, Li W, Hu L, Zeng L, Wu P, Duan L, Liu Z.

A summary of the article is shown below:

In tumor cells, p53 is always inactivated due to the mutation or deletion of TP53 gene or inhibited by the overexpressed MDM2. Small-molecule induced restoring of p53 function by blocking MDM2-p53 protein-protein interactions has been highly pursued as an attractive therapeutic strategy for cancer therapy. To date, a large number of small-molecule inhibitors have been identified based on the compact and well-defined MDM2-p53 interactions, of which SAR405838, MK-8242, DS-3032b, NVP-CGM097, RG7112, HDM201, RG7388, ALRN-6924 and AMG 232 are undergoing clinical assessment at different phases for cancer therapy. This review is focused on the discovery and development of piperidinone-based MDM2-p53 inhibitors for cancer therapy, including the identification of hit compounds, hit-to-lead optimizations, binding models of ligands in the active site of MDM2, metabolic studies, and preclinical data of advanced piperidinone-based MDM2-p53 inhibitors. Additionally, acquired resistance of MDM2 inhibitors and potential toxicity toward normal tissues are briefly discussed.

Check out the article’s website on Pubmed for more information:



This article is a good source of information and a good way to become familiar with topics such as:

AMG-232;Cancer therapy;MDM2 inhibitors;MDM2-p53 interactions;Piperidinones

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