4r5y
From Proteopedia
(Difference between revisions)
| Line 4: | Line 4: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4r5y]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R5Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R5Y FirstGlance]. <br> | <table><tr><td colspan='2'>[[4r5y]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R5Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R5Y FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3K3:5-({(1R,1AS,6BR)-1-[5-(TRIFLUOROMETHYL)-1H-BENZIMIDAZOL-2-YL]-1A,6B-DIHYDRO-1H-CYCLOPROPA[B][1]BENZOFURAN-5-YL}OXY)-3,4-DIHYDRO-1,8-NAPHTHYRIDIN-2(1H)-ONE'>3K3</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3K3:5-({(1R,1AS,6BR)-1-[5-(TRIFLUOROMETHYL)-1H-BENZIMIDAZOL-2-YL]-1A,6B-DIHYDRO-1H-CYCLOPROPA[B][1]BENZOFURAN-5-YL}OXY)-3,4-DIHYDRO-1,8-NAPHTHYRIDIN-2(1H)-ONE'>3K3</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4r5y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5y OCA], [https://pdbe.org/4r5y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r5y RCSB], [https://www.ebi.ac.uk/pdbsum/4r5y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r5y ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4r5y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5y OCA], [https://pdbe.org/4r5y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r5y RCSB], [https://www.ebi.ac.uk/pdbsum/4r5y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r5y ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| Line 11: | Line 12: | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN] Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron. | [https://www.uniprot.org/uniprot/BRAF_HUMAN BRAF_HUMAN] Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron. | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Oncogenic BRAF, which drives cell transformation and proliferation, has been detected in approximately 50% of human malignant melanomas and 5% to 15% of colorectal cancers. Despite the remarkable clinical activities achieved by vemurafenib and dabrafenib in treating BRAF(V600E) metastatic melanoma, their clinical efficacy in BRAF(V600E) colorectal cancer is far less impressive. Prior studies suggested that feedback activation of EGFR and MAPK signaling upon BRAF inhibition might contribute to the relative unresponsiveness of colorectal cancer to the first-generation BRAF inhibitors. Here, we report characterization of a dual RAF kinase/EGFR inhibitor, BGB-283, which is currently under clinical investigation. In vitro, BGB-283 potently inhibits BRAF(V600E)-activated ERK phosphorylation and cell proliferation. It demonstrates selective cytotoxicity and preferentially inhibits proliferation of cancer cells harboring BRAF(V600E) and EGFR mutation/amplification. In BRAF(V600E) colorectal cancer cell lines, BGB-283 effectively inhibits the reactivation of EGFR and EGFR-mediated cell proliferation. In vivo, BGB-283 treatment leads to dose-dependent tumor growth inhibition accompanied by partial and complete tumor regressions in both cell line-derived and primary human colorectal tumor xenografts bearing BRAF(V600E) mutation. These findings support BGB-283 as a potent antitumor drug candidate with clinical potential for treating colorectal cancer harboring BRAF(V600E) mutation. | ||
| - | |||
| - | BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor Activity in BRAF-Mutated Colorectal Cancers.,Tang Z, Yuan X, Du R, Cheung SH, Zhang G, Wei J, Zhao Y, Feng Y, Peng H, Zhang Y, Du Y, Hu X, Gong W, Liu Y, Gao Y, Liu Y, Hao R, Li S, Wang S, Ji J, Zhang L, Li S, Sutton D, Wei M, Zhou C, Wang L, Luo L Mol Cancer Ther. 2015 Oct;14(10):2187-97. doi: 10.1158/1535-7163.MCT-15-0262., Epub 2015 Jul 24. PMID:26208524<ref>PMID:26208524</ref> | ||
| - | |||
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4r5y" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
The complex structure of Braf V600E kinase domain with a novel Braf inhibitor
| |||||||||||
Categories: Homo sapiens | Large Structures | Feng Y | Liu Y | Peng H | Wei M | Zhang Y
