In vitro and in vivo characterization of a novel, highly potent p53-MDM2 inhibitor.
Bioorg Med Chem Lett
; 28(20): 3404-3408, 2018 11 01.
Article
em En
| MEDLINE
| ID: mdl-30217415
ABSTRACT
Small molecule inhibitors of the p53-MDM2 protein complex are under intense investigation in clinical trials as anti-cancer agents, including our first generation inhibitor NVP-CGM097. We recently described the rational design of a novel pyrazolopyrrolidinone core as a new lead structure and now we report on the synthesis and optimization of this to provide a highly potent lead compound. This new compound displayed excellent oral efficacy in our preclinical mechanistic in vivo model and marked a significant milestone towards the identification of our second generation clinical candidate NVP-HDM201.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Pirazóis
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Pirrolidinonas
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Proteína Supressora de Tumor p53
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Proteínas Proto-Oncogênicas c-mdm2
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Multimerização Proteica
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Antineoplásicos
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article