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[[Image:3spf.jpg|left|200px]]
==Crystal Structure of Bcl-xL bound to BM501==
<StructureSection load='3spf' size='340' side='right' caption='[[3spf]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3spf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SPF FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B50:4-(4-CHLOROPHENYL)-1-[(3S)-3,4-DIHYDROXYBUTYL]-N-[3-(4-METHYLPIPERAZIN-1-YL)PROPYL]-3-PHENYL-1H-PYRROLE-2-CARBOXAMIDE'>B50</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene><br>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3sp7|3sp7]]</td></tr>
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Bcl-xL, BCL2L, BCL2L1, BCLX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3spf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3spf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3spf RCSB], [http://www.ebi.ac.uk/pdbsum/3spf PDBsum]</span></td></tr>
<table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Employing a structure-based strategy, we have designed a new class of potent small-molecule inhibitors of the anti-apoptotic proteins Bcl-2 and Bcl-xL. An initial lead compound with a new scaffold was designed based upon the crystal structure of Bcl-xL and U.S. Food and Drug Administration (FDA) approved drugs and was found to have an affinity of 100 muM for both Bcl-2 and Bcl-xL. Linking this weak lead to another weak-affinity fragment derived from Abbott's ABT-737 led to an improvement of the binding affinity by a factor of &gt;10 000. Further optimization ultimately yielded compounds with subnanomolar binding affinities for both Bcl-2 and Bcl-xL and potent cellular activity. The best compound (21) binds to Bcl-xL and Bcl-2 with K(i) &lt; 1 nM, inhibits cell growth in the H146 and H1417 small-cell lung cancer cell lines with IC(50) values of 60-90 nM, and induces robust cell death in the H146 cancer cell line at 30-100 nM.


{{STRUCTURE_3spf|  PDB=3spf  |  SCENE=  }}
Design of Bcl-2 and Bcl-xL Inhibitors with Subnanomolar Binding Affinities Based upon a New Scaffold.,Zhou H, Chen J, Meagher JL, Yang CY, Aguilar A, Liu L, Bai L, Cong X, Cai Q, Fang X, Stuckey JA, Wang S J Med Chem. 2012 May 24;55(10):4664-82. Epub 2012 May 10. PMID:22448988<ref>PMID:22448988</ref>


===Crystal Structure of Bcl-xL bound to BM501===
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
 
</div>
{{ABSTRACT_PUBMED_22448988}}
== References ==
 
<references/>
==About this Structure==
__TOC__
[[3spf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SPF OCA].
</StructureSection>
 
==Reference==
<ref group="xtra">PMID:022448988</ref><references group="xtra"/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Meagher, J L.]]
[[Category: Meagher, J L.]]
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