Document Detail


A selective inhibitor reveals PI3Kγ dependence of T(H)17 cell differentiation.
MedLine Citation:
PMID:  22544264     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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; 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
Related Documents :
10678094 - Apoptosis and necrosis induced by sulfur mustard in hela cells.
17486684 - Effects of propolis extract on sensitivity to chemotherapeutic agents in hela and resis...
8180964 - Effect of selenite on tumor cell invasiveness.
6900354 - The effect of exogenous adenosine triphosphate on potassium movements in hela cells.
19003024 - Influence of glucose starvation on the pathway of death in insect cell line sl: apoptos...
24963324 - Antitumor effects and biological mechanism of action of the aqueous extract of the camp...
Publication Detail:
Type:  Journal Article     Date:  2012-04-29
Journal Detail:
Title:  Nature chemical biology     Volume:  8     ISSN:  1552-4469     ISO Abbreviation:  Nat. Chem. Biol.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-23     Completed Date:  2012-07-16     Revised Date:  2012-10-11    
Medline Journal Info:
Nlm Unique ID:  101231976     Medline TA:  Nat Chem Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  576-82     Citation Subset:  IM    
Affiliation:
Cellzome AG, Heidelberg, Germany.
Data Bank Information
Bank Name/Acc. No.:
PDB/4AOF; PubChem-Substance/135631865;  135631866;  135631867;  135631868;  135631869;  135631870;  135631871;  135631872;  135631873;  135631874;  135631875;  135631876;  135631877;  135631878;  135631879;  135631880;  135631881;  135631882;  135631883;  135631884;  135631885;  135631886;  135631887;  135631888;  135631889;  135631890;  135631891;  135631892;  135631893;  135631894;  135631895;  135631896;  135631897;  135631898;  135631899;  135631900;  135631901;  135631902;  135631903;  135631904;  135631905;  135631906;  135631907;  135631914;  135631915;  135631916;  135631917;  135631918;  135631919;  135631920;  135631921;  135631922;  135631923;  135631924;  135631925;  135631926;  135631927;  135631928;  135631929;  135631930;  135631931;  135631932;  135631933;  135631934;  135631935;  135631936;  135631937;  135631938;  135631939;  135631940;  135631941;  135631942;  135631943;  135631944;  135631945;  135631946;  135631947;  135631948;  135631949;  135631950;  135631951;  135631952;  135631953;  135631954;  135631955;  135631956;  135631957;  135631958;  135631959;  135631960
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents, Non-Steroidal / chemistry,  pharmacokinetics,  pharmacology*,  therapeutic use
Arthritis, Experimental / drug therapy,  immunology,  pathology
Binding, Competitive
Cell Differentiation / drug effects*
Cell Line
Cell Movement / drug effects
Class Ib Phosphatidylinositol 3-Kinase / antagonists & inhibitors*
Drug Discovery
Enzyme Inhibitors / chemistry,  pharmacokinetics,  pharmacology*,  therapeutic use
Humans
Interleukin-17 / immunology*
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Molecular Structure
Rats
Rats, Wistar
Small Molecule Libraries / chemistry,  pharmacokinetics,  pharmacology*,  therapeutic use
Structure-Activity Relationship
T-Lymphocytes, Helper-Inducer / cytology,  drug effects*,  enzymology,  immunology
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Enzyme Inhibitors; 0/Interleukin-17; 0/Small Molecule Libraries; EC 2.7.1.137/Class Ib Phosphatidylinositol 3-Kinase; EC 2.7.1.137/PIK3CG protein, human; EC 2.7.1.153/Pik3cg protein, mouse
Comments/Corrections
Erratum In:
Nat Chem Biol. 2012 Aug;8(8):737

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Prospective study of HBV reactivation risk in rheumatoid arthritis patients who received conventiona...
Next Document:  MexT functions as a redox-responsive regulator modulating disulfide stress resistance in Pseudomonas...