2. Academic Validation
  3. Development of isoform selective PI3-kinase inhibitors as pharmacological tools for elucidating the PI3K pathway

Development of isoform selective PI3-kinase inhibitors as pharmacological tools for elucidating the PI3K pathway

  • Bioorg Med Chem Lett. 2012 Sep 1;22(17):5445-50. doi: 10.1016/j.bmcl.2012.07.042.
Ian Bruce 1,  Mohammed Akhlaq,  Graham C Bloomfield,  Emma Budd,  Brian Cox,  Bernard Cuenoud,  Peter Finan,  Peter Gedeck,  Julia Hatto,  Judy F Hayler,  Denise Head,  Thomas Keller,  Louise Kirman,  Catherine Leblanc,  Darren Le Grand,  Clive McCarthy,  Desmond O'Connor,  Charles Owen,  Mrinalini S Oza,  Gaynor Pilgrim,  Nicola E Press,  Lilya Sviridenko,  Lewis Whitehead
Affiliations

Affiliation

  • 1 Novartis Institutes for Biomedical Research, Respiratory Disease Area, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK. [email protected]
PMID: 22863202 DOI: 10.1016/j.bmcl.2012.07.042
Abstract

Using a parallel synthesis approach to target a non-conserved region of the PI3K catalytic domain a pan-PI3K inhibitor 1 was elaborated to provide alpha, delta and gamma isoform selective Class I PI3K inhibitors 21, 24, 26 and 27. The compounds had good cellular activity and were selective against protein kinases and other members of the PI3K superfamily including mTOR and DNA-PK.

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