Jay F Davies

Publications (2)7.45 Total impact

• Article: Dihydroxyphenylisoindoline amides as orally bioavailable inhibitors of the heat shock protein 90 (hsp90) molecular chaperone.

  Pei-Pei Kung, Buwen Huang, Gang Zhang, Joe Zhongxiang Zhou, Jeff Wang, Jennifer A Digits, Judith Skaptason, Shinji Yamazaki, David Neul, Michael Zientek, Jeff Elleraas, Pramod Mehta, Min-Jean Yin, Michael J Hickey, Ketan S Gajiwala, Caroline Rodgers, Jay F Davies, Michael R Gehring
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  ABSTRACT: The discovery and optimization of potency and metabolic stability of a novel class of dihyroxyphenylisoindoline amides as Hsp90 inhibitors are presented. Optimization of a screening hit using structure-based design and modification of log D and chemical structural features led to the identification of a class of orally bioavailable non-quinone-containing Hsp90 inhibitors. This class is exemplified by 14 and 15, which possess improved cell potency and pharmacokinetic profiles compared with the original screening hit.
  Journal of Medicinal Chemistry 11/2009; 53(1):499-503. · 4.80 Impact Factor
• Article: Dihydroxylphenyl amides as inhibitors of the Hsp90 molecular chaperone.

  Pei-Pei Kung, Lee Funk, Jerry Meng, Michael Collins, Joe Zhongxiang Zhou, M Catherine Johnson, Anne Ekker, Jeff Wang, Pramod Mehta, Min-Jean Yin, Caroline Rodgers, Jay F Davies, Eileen Bayman, Tod Smeal, Karen A Maegley, Michael R Gehring
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  ABSTRACT: Information from X-ray crystal structures were used to optimize the potency of a HTS hit in a Hsp90 competitive binding assay. A class of novel and potent small molecule Hsp90 inhibitors were thereby identified. Enantio-pure compounds 31 and 33 were potent in PGA-based competitive binding assay and inhibited proliferation of various human cancer cell lines in vitro, with IC(50) values averaging 20 nM.
  Bioorganic & medicinal chemistry letters 10/2008; 18(23):6273-8. · 2.65 Impact Factor