View source for 9eue


==The FK1 domain of FKBP51 in complex with SAFit-analog 23a==
<StructureSection load='9eue' size='340' side='right'caption='[[9eue]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9eue]] 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=9EUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9EUE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1H68:(1-methylpyrazol-4-yl)methyl+(2S)-1-[(2S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)ethanoyl]piperidine-2-carboxylate'>A1H68</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=9eue FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9eue OCA], [https://pdbe.org/9eue PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9eue RCSB], [https://www.ebi.ac.uk/pdbsum/9eue PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9eue ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The FK506 binding protein 51 (FKBP51) is an appealing drug target due to its role in several diseases such as depression, anxiety, chronic pain and obesity. Towards this, selectivity versus the close homolog FKBP52 is essential. However, currently available FKBP51-selective ligands such as SAFit2 are too large and lack drug-like properties. Here, we present a structure activity relationship (SAR) analysis of the pipecolic ester moiety of SAFit1 and SAFit2, which culminated in the discovery of the 1,4-pyrazolyl derivative 23d, displaying a binding affinity of 0.077 microM for FKBP51, reduced molecular weight (541.7 g/mol), lower hydrophobicity (cLogP = 3.72) and higher ligand efficiency (LE = 0.25). Cocrystal structures revealed the importance of the 1,4- and 1,3,4- substitution patterns of the pyrazole ring versus the 1,4,5 arrangement.

1,4-Pyrazolyl-containing SAFit-analogues are selective FKBP51 inhibitors with improved ligand efficiency and drug-like profile.,Buffa V, Meyners C, Sugiarto WO, Bauder M, Gaali S, Hausch F ChemMedChem. 2024 May 31:e202400264. doi: 10.1002/cmdc.202400264. PMID:38818693<ref>PMID:38818693</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9eue" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Buffa V]]
[[Category: Hausch F]]
[[Category: Meyners C]]