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A Selective Inhibitor Reveals PI3Kγ Dependence of T(H)17 Cell Differentiation

Giovanna Bergamini, Kathryn Bell, Satoko Shimamura, Thilo Werner, Andrew Cansfield, Katrin Müller, Jessica Perrin, Christina Rau, Katie Ellard, Carsten Hopf, Carola Doce, Daniel Leggate, Raffaella Mangano, etc.

Nat Chem Biol. 2012 Apr 29;8(6):576-82.

PMID: 22544264

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP1159824675 CZC24832 CZC24832 1159824-67-5 Price
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