2rfs: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,330,058 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,330,058 edits
No edit summary
Line 1: Line 1:
[[Image:2rfs.jpg|left|200px]]
{{Seed}}
[[Image:2rfs.png|left|200px]]


<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2rfs|  PDB=2rfs  |  SCENE=  }}  
{{STRUCTURE_2rfs|  PDB=2rfs  |  SCENE=  }}  


'''X-ray structure of SU11274 bound to c-Met'''
===X-ray structure of SU11274 bound to c-Met===




==Overview==
<!--
c-Met is a receptor tyrosine kinase often deregulated in human cancers, thus making it an attractive drug target. One mechanism by which c-Met deregulation leads to cancer is through gain-of-function mutations. Therefore, small molecules capable of targeting these mutations could offer therapeutic benefits for affected patients. SU11274 was recently described and reported to inhibit the activity of the wild-type and some mutant forms of c-Met, whereas other mutants are resistant to inhibition. We identified a novel series of c-Met small molecule inhibitors that are active against multiple mutants previously identified in hereditary papillary renal cell carcinoma patients. AM7 is active against wild-type c-Met as well as several mutants, inhibits c-Met-mediated signaling in MKN-45 and U-87 MG cells, and inhibits tumor growth in these two models grown as xenografts. The crystal structures of AM7 and SU11274 bound to unphosphorylated c-Met have been determined. The AM7 structure reveals a novel binding mode compared with other published c-Met inhibitors and SU11274. The molecule binds the kinase linker and then extends into a new hydrophobic binding site. This binding site is created by a significant movement of the C-helix and so represents an inactive conformation of the c-Met kinase. Thus, our results demonstrate that it is possible to identify and design inhibitors that will likely be active against mutants found in different cancers.
The line below this paragraph, {{ABSTRACT_PUBMED_18055465}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 18055465 is the PubMed ID number.
-->
{{ABSTRACT_PUBMED_18055465}}


==Disease==
==Disease==
Line 44: Line 48:
[[Category: Transmembrane]]
[[Category: Transmembrane]]
[[Category: Tyrosine-protein kinase]]
[[Category: Tyrosine-protein kinase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 16 23:08:16 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 16:02:51 2008''

Revision as of 13:02, 27 July 2008

File:2rfs.png

Template:STRUCTURE 2rfs

X-ray structure of SU11274 bound to c-Met

Template:ABSTRACT PUBMED 18055465

Disease

Known disease associated with this structure: Hepatocellular carcinoma, childhood type OMIM:[164860], Renal cell carcinoma, papillary, familial and sporadic OMIM:[164860], Autism, suseptibility to, 9 OMIM:[164860]

About this Structure

2RFS is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

c-Met inhibitors with novel binding mode show activity against several hereditary papillary renal cell carcinoma-related mutations., Bellon SF, Kaplan-Lefko P, Yang Y, Zhang Y, Moriguchi J, Rex K, Johnson CW, Rose PE, Long AM, O'Connor AB, Gu Y, Coxon A, Kim TS, Tasker A, Burgess TL, Dussault I, J Biol Chem. 2008 Feb 1;283(5):2675-83. Epub 2007 Nov 30. PMID:18055465

Page seeded by OCA on Sun Jul 27 16:02:51 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "https://proteopedia.org/index.php?title=2rfs&oldid=654815"