1,4-Benzodiazepine-2,5-diones as small molecule antagonists of the HDM2–p53 interaction: discovery and SAR

Autor:	Jennifer Lattanze, Tianbao Lu, Karen L. Milkiewicz, Bruce L. Grasberger, Theodore E. Carver, Louis V. LaFrance, Daniel J. Parks, Kannan Ramachandren, Varsha Gupta, Raul R. Calvo, Diane M. Maguire, Eugene C. Petrella, Maxwell D. Cummings
Rok vydání:	2005
Předmět:	medicine.drug_class Stereochemistry Carboxylic acid Clinical Biochemistry Pharmaceutical Science Fluorescence Polarization Peptide Biochemistry Chemical synthesis Benzodiazepines Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound Proto-Oncogene Proteins Drug Discovery medicine Combinatorial Chemistry Techniques Humans Binding site Molecular Biology chemistry.chemical_classification Benzodiazepine Binding Sites Organic Chemistry Nuclear Proteins Proto-Oncogene Proteins c-mdm2 Small molecule chemistry Lactam Molecular Medicine Tumor Suppressor Protein p53 Fluorescence anisotropy Protein Binding
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 15:765-770
ISSN:	0960-894X
Popis:	A library of 1,4-benzodiazepine-2,5-diones was screened for binding to the p53-binding domain of HDM2 using Thermofluor ® , a miniaturized thermal denaturation assay. The hits obtained were shown to bind to HDM2 in the p53-binding pocket using a fluorescence polarization (FP) peptide displacement assay. The potency of the series was optimized, leading to sub-micromolar antagonists of the p53–HDM2 interaction.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eed49474f88d1fb7a63d4bf5e23b6ee3 https://doi.org/10.1016/j.bmcl.2004.11.009 Zobrazit plný text záznamu Full Text from ScienceDirect