2og8: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2og8.jpg|left|200px]] | [[Image:2og8.jpg|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_2og8", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
or leave the SCENE parameter empty for the default display. | |||
| | --> | ||
| | {{STRUCTURE_2og8| PDB=2og8 | SCENE= }} | ||
}} | |||
'''crystal structure of aminoquinazoline 36 bound to Lck''' | '''crystal structure of aminoquinazoline 36 bound to Lck''' | ||
| Line 30: | Line 27: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Huang, X.]] | [[Category: Huang, X.]] | ||
[[Category: | [[Category: Kinase domain]] | ||
[[Category: | [[Category: Lck]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:50:51 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 10:50, 4 May 2008
crystal structure of aminoquinazoline 36 bound to Lck
OverviewOverview
The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and natural killer (NK) cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. Selective inhibition of Lck is expected to offer a new therapy for the treatment of T-cell-mediated autoimmune and inflammatory disease. Screening of our kinase-preferred collection identified aminoquinazoline 1 as a potent, nonselective inhibitor of Lck and T cell proliferation. In this report, we describe the synthesis and structure-activity relationships of a series of novel aminoquinazolines possessing in vitro mechanism-based potency. Optimized, orally bioavailable compounds 32 and 47 exhibit anti-inflammatory activity (ED(50) of 22 and 11 mg/kg, respectively) in the anti-CD3-induced production of interleukin-2 (IL-2) in mice.
DiseaseDisease
Known disease associated with this structure: SCID due to LCK deficiency OMIM:[153390]
About this StructureAbout this Structure
2OG8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Discovery of aminoquinazolines as potent, orally bioavailable inhibitors of Lck: synthesis, SAR, and in vivo anti-inflammatory activity., DiMauro EF, Newcomb J, Nunes JJ, Bemis JE, Boucher C, Buchanan JL, Buckner WH, Cee VJ, Chai L, Deak HL, Epstein LF, Faust T, Gallant P, Geuns-Meyer SD, Gore A, Gu Y, Henkle B, Hodous BL, Hsieh F, Huang X, Kim JL, Lee JH, Martin MW, Masse CE, McGowan DC, Metz D, Mohn D, Morgenstern KA, Oliveira-dos-Santos A, Patel VF, Powers D, Rose PE, Schneider S, Tomlinson SA, Tudor YY, Turci SM, Welcher AA, White RD, Zhao H, Zhu L, Zhu X, J Med Chem. 2006 Sep 21;49(19):5671-86. PMID:16970394 Page seeded by OCA on Sun May 4 10:50:51 2008