2. Academic Validation
  3. Design, structure-activity relationship, and in vivo characterization of the development candidate NVP-HSP990

Design, structure-activity relationship, and in vivo characterization of the development candidate NVP-HSP990

  • J Med Chem. 2014 Nov 13;57(21):9124-9. doi: 10.1021/jm501107q.
Christopher M McBride 1,  Barry Levine,  Yi Xia,  Cornelia Bellamacina,  Timothy Machajewski,  Zhenhai Gao,  Paul Renhowe,  William Antonios-McCrea,  Paul Barsanti,  Kristin Brinner,  Abran Costales,  Brandon Doughan,  Xiaodong Lin,  Alicia Louie,  Maureen McKenna,  Kris Mendenhall,  Daniel Poon,  Alice Rico,  Michael Wang,  Teresa E Williams,  Tinya Abrams,  Susan Fong,  Thomas Hendrickson,  Dachuan Lei,  Julie Lin,  Daniel Menezes,  Nancy Pryer,  Pietro Taverna,  Yongjin Xu,  Yasheen Zhou,  Cynthia M Shafer
Affiliations

Affiliation

  • 1 Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research , 5300 Chiron Way, Emeryville, California 94608, United States.
PMID: 25368984 DOI: 10.1021/jm501107q
Abstract

Utilizing structure-based drug design, a novel dihydropyridopyrimidinone series which exhibited potent HSP90 inhibition, good pharmacokinetics upon oral administration, and an excellent pharmacokinetic/pharmacodynamic relationship in vivo was developed from a commercial hit. The exploration of this series led to the selection of NVP-HSP990 as a development candidate.

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