View source for 4xjs


==Human CD38 complexed with inhibitor 1 [6-fluoro-2-methyl-4-[(2,3,6-trichlorobenzyl)amino]quinoline-8-carboxamide]==
<StructureSection load='4xjs' size='340' side='right'caption='[[4xjs]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4xjs]] is a 1 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=4XJS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XJS 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=733:6-FLUORO-2-METHYL-4-[(2,3,6-TRICHLOROBENZYL)AMINO]QUINOLINE-8-CARBOXAMIDE'>733</scene>, <scene name='pdbligand=HSX:5-O-PHOSPHONO-ALPHA-D-RIBOFURANOSE'>HSX</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=4xjs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xjs OCA], [https://pdbe.org/4xjs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xjs RCSB], [https://www.ebi.ac.uk/pdbsum/4xjs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xjs ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CD38_HUMAN CD38_HUMAN] Synthesizes cyclic ADP-ribose, a second messenger for glucose-induced insulin secretion. Also has cADPr hydrolase activity. Also moonlights as a receptor in cells of the immune system.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Starting from the micromolar 8-quinoline carboxamide high-throughput screening hit 1a, a systematic exploration of the structure-activity relationships (SAR) of the 4-, 6-, and 8-substituents of the quinoline ring resulted in the identification of approximately 10-100-fold more potent human CD38 inhibitors. Several of these molecules also exhibited pharmacokinetic parameters suitable for in vivo animal studies, including low clearances and decent oral bioavailability. Two of these CD38 inhibitors, 1ah and 1ai, were shown to elevate NAD tissue levels in liver and muscle in a diet-induced obese (DIO) C57BL/6 mouse model. These inhibitor tool compounds will enable further biological studies of the CD38 enzyme as well as the investigation of the therapeutic implications of NAD enhancement in disease models of abnormally low NAD.

Discovery of 4-Amino-8-quinoline Carboxamides as Novel, Submicromolar Inhibitors of NAD-Hydrolyzing Enzyme CD38.,Becherer JD, Boros EE, Carpenter TY, Cowan DJ, Deaton DN, Haffner CD, Jeune MR, Kaldor IW, Poole JC, Preugschat F, Rheault TR, Schulte CA, Shearer BG, Shearer TW, Shewchuk LM, Smalley TL Jr, Stewart EL, Stuart JD, Ulrich JC J Med Chem. 2015 Aug 24. PMID:26267483<ref>PMID:26267483</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4xjs" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Deaton D]]
[[Category: Shewchuk LM]]
[[Category: Stewart E]]