平方毫米
临床试验
医学
癌症研究
癌症
小分子
肿瘤科
药理学
生物信息学
内科学
生物
遗传学
细胞培养
作者
Marina Konopleva,Giovanni Martinelli,Naval Daver,Cristina Papayannidis,Andrew H. Wei,Brian Higgins,Marion Ott,John Mascarenhas,Michael Andreeff
出处
期刊:Leukemia
[Springer Nature]
日期:2020-07-10
卷期号:34 (11): 2858-2874
被引量:239
标识
DOI:10.1038/s41375-020-0949-z
摘要
Targeting the interaction between tumor suppressor p53 and the E3 ligase MDM2 represents an attractive treatment approach for cancers with wild-type or functional TP53. Indeed, several small molecules have been developed and evaluated in various malignancies. We provide an overview of MDM2 inhibitors under preclinical and clinical investigation, with a focus on molecules with ongoing clinical trials, as indicated by ClinicalTrials.gov . Because preclinical and clinical exploration of combination strategies is underway, data supporting these combinations are also described. We identified the following molecules for inclusion in this review: RG7112 (RO5045337), idasanutlin (RG7388), AMG-232 (KRT-232), APG-115, BI-907828, CGM097, siremadlin (HDM201), and milademetan (DS-3032b). Information about each MDM2 inhibitor was collected from major congress records and PubMed using the following search terms: each molecule name, MDM2and HDM2. Only congress records were limited by date (January 1, 2012-March 6, 2020). Special attention was given to available data in hematologic malignancies; however, available safety data in any indication are reported. Overall, targeting MDM2 is a promising treatment strategy, as evidenced by the increasing number of MDM2 inhibitors entering the clinic. Additional clinical investigation is needed to further elucidate the role of MDM2 inhibitors in the treatment of human cancers.
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