2. Academic Validation
  3. A selective inhibitor reveals PI3Kγ dependence of T(H)17 cell differentiation

A selective inhibitor reveals PI3Kγ dependence of T(H)17 cell differentiation

  • Nat Chem Biol. 2012 Apr 29;8(6):576-82. doi: 10.1038/nchembio.957.
Giovanna Bergamini 1,  Kathryn Bell,  Satoko Shimamura,  Thilo Werner,  Andrew Cansfield,  Katrin Müller,  Jessica Perrin,  Christina Rau,  Katie Ellard,  Carsten Hopf,  Carola Doce,  Daniel Leggate,  Raffaella Mangano,  Toby Mathieson,  Alison O'Mahony,  Ivan Plavec,  Faiza Rharbaoui,  Friedrich Reinhard,  Mikhail M Savitski,  Nigel Ramsden,  Emilio Hirsch,  Gerard Drewes,  Oliver Rausch,  Marcus Bantscheff,  Gitte Neubauer
Affiliations

Affiliation

  • 1 Cellzome AG, Heidelberg, Germany.
PMID: 22544264 DOI: 10.1038/nchembio.957
Abstract

We devised a high-throughput chemoproteomics method that enabled multiplexed screening of 16,000 compounds against native protein and lipid kinases in cell extracts. Optimization of one chemical series resulted in CZC24832, which is to our knowledge the first selective inhibitor of phosphoinositide 3-kinase γ (PI3Kγ) with efficacy in in vitro and in vivo models of inflammation. Extensive target- and cell-based profiling of CZC24832 revealed regulation of interleukin-17-producing T helper cell (T(H)17) differentiation by PI3Kγ, thus reinforcing selective inhibition of PI3Kγ as a potential treatment for inflammatory and autoimmune diseases.

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