4oq5

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2UU:4-(4-METHYLNAPHTHALEN-1-YL)-2-{[(4-PHENOXYPHENYL)SULFONYL]AMINO}BENZOIC+ACID'>2UU</scene></td></tr>

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

Apoptosis is regulated by the BCL-2 family of proteins, which is comprised of both pro-death and pro-survival members. Evasion of apoptosis is a hallmark of malignant cells. One way in which cancer cells achieve this evasion is thru overexpression of the pro-survival members of the BCL-2 family. Overexpression of MCL-1, a pro-survival protein, has been shown to be a resistance factor for Navitoclax, a potent inhibitor of BCL-2 and BCL-XL. Here we describe the use of fragment screening methods and structural biology to drive the discovery of novel MCL-1 inhibitors from two distinct structural classes. Specifically, cores derived from a biphenyl sulfonamide and salicylic acid were uncovered in an NMR-based fragment screen and elaborated using high throughput analog synthesis. This culminated in the discovery of selective and potent inhibitors of MCL-1 that may serve as promising leads for medicinal chemistry optimization efforts.

Fragment-based discovery of potent inhibitors of the anti-apoptotic MCL-1 protein.,Petros AM, Swann SL, Song D, Swinger K, Park C, Zhang H, Wendt MD, Kunzer AR, Souers AJ, Sun C Bioorg Med Chem Lett. 2014 Mar 15;24(6):1484-8. doi: 10.1016/j.bmcl.2014.02.010. , Epub 2014 Feb 14. PMID:24582986<ref>PMID:24582986</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

</div>

<div class="pdbe-citations 4oq5" style="background-color:#fffaf0;"></div>