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| [[Image:2a4z.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_2a4z| PDB=2a4z | SCENE= }} | | {{STRUCTURE_2a4z| PDB=2a4z | SCENE= }} |
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| '''Crystal Structure of human PI3Kgamma complexed with AS604850'''
| | ===Crystal Structure of human PI3Kgamma complexed with AS604850=== |
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| ==Overview==
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| Phosphoinositide 3-kinases (PI3K) have long been considered promising drug targets for the treatment of inflammatory and autoimmune disorders as well as cancer and cardiovascular diseases. But the lack of specificity, isoform selectivity and poor biopharmaceutical profile of PI3K inhibitors have so far hampered rigorous disease-relevant target validation. Here we describe the identification and development of specific, selective and orally active small-molecule inhibitors of PI3Kgamma (encoded by Pik3cg). We show that Pik3cg(-/-) mice are largely protected in mouse models of rheumatoid arthritis; this protection correlates with defective neutrophil migration, further validating PI3Kgamma as a therapeutic target. We also describe that oral treatment with a PI3Kgamma inhibitor suppresses the progression of joint inflammation and damage in two distinct mouse models of rheumatoid arthritis, reproducing the protective effects shown by Pik3cg(-/-) mice. Our results identify selective PI3Kgamma inhibitors as potential therapeutic molecules for the treatment of chronic inflammatory disorders such as rheumatoid arthritis.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16127437}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16127437 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16127437}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Pi3kg]] | | [[Category: Pi3kg]] |
| [[Category: Protein-inhibitor complex]] | | [[Category: Protein-inhibitor complex]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:36:27 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 09:48:41 2008'' |
