MDM2 inhibition: an important step forward in cancer therapy.
Animals
Antineoplastic Agents
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Disease Management
Disease Susceptibility
Drug Development
Enzyme Inhibitors
/ administration & dosage
Humans
Molecular Targeted Therapy
Neoplasms
/ diagnosis
Protein Binding
Proto-Oncogene Proteins c-mdm2
/ antagonists & inhibitors
Signal Transduction
Structure-Activity Relationship
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
28
04
2020
accepted:
23
06
2020
revised:
11
06
2020
pubmed:
12
7
2020
medline:
1
12
2020
entrez:
12
7
2020
Statut:
ppublish
Résumé
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, "MDM2"and "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.
Identifiants
pubmed: 32651541
doi: 10.1038/s41375-020-0949-z
pii: 10.1038/s41375-020-0949-z
doi:
Substances chimiques
Antineoplastic Agents
0
Enzyme Inhibitors
0
Proto-Oncogene Proteins c-mdm2
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2858-2874Références
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