2. Academic Validation
  3. Potent and selective inhibitors of PI3Kδ: obtaining isoform selectivity from the affinity pocket and tryptophan shelf

Potent and selective inhibitors of PI3Kδ: obtaining isoform selectivity from the affinity pocket and tryptophan shelf

  • Bioorg Med Chem Lett. 2012 Jul 1;22(13):4296-302. doi: 10.1016/j.bmcl.2012.05.027.
Daniel P Sutherlin 1,  Stewart Baker,  Angelina Bisconte,  Paul M Blaney,  Anthony Brown,  Bryan K Chan,  David Chantry,  Georgette Castanedo,  Paul DePledge,  Paul Goldsmith,  David M Goldstein,  Timothy Hancox,  Jasmit Kaur,  David Knowles,  Rama Kondru,  John Lesnick,  Matthew C Lucas,  Cristina Lewis,  Jeremy Murray,  Alan J Nadin,  Jim Nonomiya,  Jodie Pang,  Neil Pegg,  Steve Price,  Karin Reif,  Brian S Safina,  Laurent Salphati,  Steven Staben,  Eileen M Seward,  Stephen Shuttleworth,  Sukhjit Sohal,  Zachary K Sweeney,  Mark Ultsch,  Bohdan Waszkowycz,  Binqing Wei
Affiliations

Affiliation

  • 1 Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. sutherd1@gene.com
PMID: 22672799 DOI: 10.1016/j.bmcl.2012.05.027
Abstract

A potent inhibitor of PI3Kδ that is ≥ 200 fold selective for the remaining three Class I PI3K isoforms and additional kinases is described. The hypothesis for selectivity is illustrated through structure activity relationships and crystal structures of compounds bound to a K802T mutant of PI3Kγ. Pharmacokinetic data in rats and mice support the use of 3 as a useful tool compound to use for in vivo studies.

Figures
Products