Discovery of NMS-E973 as novel, selective and potent inhibitor of heat shock protein 90 (Hsp90)
Copyright policy )Discovery of NMS-E973 as novel, selective and potent inhibitor of heat shock protein 90 (Hsp90)
Novel small molecule inhibitors of heat shock protein 90 (Hsp90) were discovered with the help of a fragment based drug discovery approach (FBDD) and subsequent optimization with a combination of structure guided design, parallel synthesis and application of medicinal chemistry principles. These efforts led to the identification of compound 18 (NMS-E973), which displayed significant efficacy in a human ovarian A2780 xenograft tumor model, with a mechanism of action confirmed in vivo by typical modulation of known Hsp90 client proteins, and with a favorable pharmacokinetic and safety profile.
- University of Dundee United Kingdom
- Nerviano Medical Sciences Italy
/dk/atira/pure/subjectarea/asjc/1300/1313, /dk/atira/pure/subjectarea/asjc/1300/1312, Cell Survival, Anti-cancer agents, Drug Evaluation, Preclinical, Fragment based drug discovery, 610, Mice, Nude, Antineoplastic Agents, name=Clinical Biochemistry, Tumor cell proliferation inhibition, Crystallography, X-Ray, Mice, Structure-Activity Relationship, Catalytic Domain, Cell Line, Tumor, name=Molecular Medicine, Biomarkers, Tumor, Animals, Humans, HSP90 Heat-Shock Proteins, name=Pharmaceutical Science, Ovarian Neoplasms, /dk/atira/pure/subjectarea/asjc/1300/1303, Mice, Inbred BALB C, Binding Sites, /dk/atira/pure/subjectarea/asjc/1600/1605, name=Biochemistry, name=Molecular Biology, Isoxazoles, 540, name=Organic Chemistry, Drug Design, Female, /dk/atira/pure/subjectarea/asjc/3000/3002, /dk/atira/pure/subjectarea/asjc/1300/1308, /dk/atira/pure/subjectarea/asjc/3000/3003, name=Drug Discovery, Protein Binding
/dk/atira/pure/subjectarea/asjc/1300/1313, /dk/atira/pure/subjectarea/asjc/1300/1312, Cell Survival, Anti-cancer agents, Drug Evaluation, Preclinical, Fragment based drug discovery, 610, Mice, Nude, Antineoplastic Agents, name=Clinical Biochemistry, Tumor cell proliferation inhibition, Crystallography, X-Ray, Mice, Structure-Activity Relationship, Catalytic Domain, Cell Line, Tumor, name=Molecular Medicine, Biomarkers, Tumor, Animals, Humans, HSP90 Heat-Shock Proteins, name=Pharmaceutical Science, Ovarian Neoplasms, /dk/atira/pure/subjectarea/asjc/1300/1303, Mice, Inbred BALB C, Binding Sites, /dk/atira/pure/subjectarea/asjc/1600/1605, name=Biochemistry, name=Molecular Biology, Isoxazoles, 540, name=Organic Chemistry, Drug Design, Female, /dk/atira/pure/subjectarea/asjc/3000/3002, /dk/atira/pure/subjectarea/asjc/1300/1308, /dk/atira/pure/subjectarea/asjc/3000/3003, name=Drug Discovery, Protein Binding
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