Estrogen receptor beta (ERβ) is an isoform of estrogen that plays a role in breast cancer. An E3 ubiquitin ligase, murine double minute 2 (MDM2), can bind to ERβ and degrade it. Virtual screening protein-protein docking studies are one the approaches be performed discover FDA-approved drugs targeting interaction ERβ-MDM2 complex. This study aimed conduct virtual 1615 compounds between as initia...

background : mdm2, e-cadherin, survivin and her2 genes are involved in the regulation of normal cell growth. however, any crucial change in their expression levels can convert a normal cell into a cancer cell. numerous studies have identified alterations of these gene expression levels in various cancers, particularly in breast cancer. thus, they may be used as diagnostic biomarkers. in this ex...

<sec>P53 is well recognized to be a tumor suppressor protein. In response the external stress or environmental perturbation, p53 can promote transcription of various target genes downstream, thus regulating cell cycle, apoptosis, DNA repair, and angiogenesis. However, activation further activated by another protein, MDM2, which negatively regulates level inverse reduces p53. This phenomen...

Preface It was, indeed, a wonderful honor to receive the G. H. A. Clowes Memorial Award and present the Clowes Lecture at the Meeting for the American Association for Cancer Research. I have been fortunate to carry out research in the area of cancer biology at a remarkable time and to have had many truly extraordinary colleagues in this field. When I began my graduate student research in 1961, ...

Inhibition of murine double minute 2 (MDM2)-p53 protein-protein interaction with small molecules has been shown to reactivate p53 and inhibit tumor growth. Here, we describe rational, structure-guided, design novel isoindolinone-based MDM2 inhibitors. X-ray crystallography, quantum mechanics ligand-based design, metabolite identification all contributed toward the discovery potent in vitro vivo...

Of the >40 alternative and aberrant splice variants of MDM2 that have been described to date, the majority has lost both the well-characterized nuclear localization signal (NLS1) and the nuclear export signal (NES) sequence. Because cellular localization of proteins provides insight regarding their potential function, we determined the localization of three different MDM2 splice variants. The s...

The tumour suppressor p53 is frequently mutated in tumours. Mutant p53 (Mutp53) proteins often gain new activities in promoting tumorigenesis, defined as gain-of-function (GOF). Mutp53 can accumulate to high levels in tumours, which promotes mutp53 GOF in tumorigenesis. The mechanism of mutp53 accumulation is poorly understood. Here we find that MDM2 isoforms promote mutp53 accumulation in tumo...

A major challenge in the field of ligand discovery is to identify chemically useful fragments that can be developed into inhibitors of specific protein-protein interactions. Low molecular weight fragments (with molecular weight less than 250 Da) are likely to bind weakly to a protein's surface. Here we use a new virtual screening procedure which uses a combination of similarity searching and do...