3c4c

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:3c4c.jpg|left|200px]]
+
{{Seed}}
 +
[[Image:3c4c.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_3c4c| PDB=3c4c | SCENE= }}
{{STRUCTURE_3c4c| PDB=3c4c | SCENE= }}
-
'''B-Raf Kinase in Complex with PLX4720'''
+
===B-Raf Kinase in Complex with PLX4720===
-
==Overview==
+
<!--
-
BRAF(V600E) is the most frequent oncogenic protein kinase mutation known. Furthermore, inhibitors targeting "active" protein kinases have demonstrated significant utility in the therapeutic repertoire against cancer. Therefore, we pursued the development of specific kinase inhibitors targeting B-Raf, and the V600E allele in particular. By using a structure-guided discovery approach, a potent and selective inhibitor of active B-Raf has been discovered. PLX4720, a 7-azaindole derivative that inhibits B-Raf(V600E) with an IC(50) of 13 nM, defines a class of kinase inhibitor with marked selectivity in both biochemical and cellular assays. PLX4720 preferentially inhibits the active B-Raf(V600E) kinase compared with a broad spectrum of other kinases, and potent cytotoxic effects are also exclusive to cells bearing the V600E allele. Consistent with the high degree of selectivity, ERK phosphorylation is potently inhibited by PLX4720 in B-Raf(V600E)-bearing tumor cell lines but not in cells lacking oncogenic B-Raf. In melanoma models, PLX4720 induces cell cycle arrest and apoptosis exclusively in B-Raf(V600E)-positive cells. In B-Raf(V600E)-dependent tumor xenograft models, orally dosed PLX4720 causes significant tumor growth delays, including tumor regressions, without evidence of toxicity. The work described here represents the entire discovery process, from initial identification through structural and biological studies in animal models to a promising therapeutic for testing in cancer patients bearing B-Raf(V600E)-driven tumors.
+
The line below this paragraph, {{ABSTRACT_PUBMED_18287029}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 18287029 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_18287029}}
==About this Structure==
==About this Structure==
Line 43: Line 47:
[[Category: Zinc]]
[[Category: Zinc]]
[[Category: Zinc-finger]]
[[Category: Zinc-finger]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 21:19:50 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:35:21 2008''

Revision as of 04:35, 28 July 2008

Image:3c4c.png

Template:STRUCTURE 3c4c

B-Raf Kinase in Complex with PLX4720

Template:ABSTRACT PUBMED 18287029

About this Structure

3C4C is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity., Tsai J, Lee JT, Wang W, Zhang J, Cho H, Mamo S, Bremer R, Gillette S, Kong J, Haass NK, Sproesser K, Li L, Smalley KS, Fong D, Zhu YL, Marimuthu A, Nguyen H, Lam B, Liu J, Cheung I, Rice J, Suzuki Y, Luu C, Settachatgul C, Shellooe R, Cantwell J, Kim SH, Schlessinger J, Zhang KY, West BL, Powell B, Habets G, Zhang C, Ibrahim PN, Hirth P, Artis DR, Herlyn M, Bollag G, Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3041-6. Epub 2008 Feb 19. PMID:18287029

Page seeded by OCA on Mon Jul 28 07:35:21 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3c4c"
Personal tools