6peb: Difference between revisions
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==Crystal Structure of human NAMPT in complex with NVP-LTM976== | |||
<StructureSection load='6peb' size='340' side='right'caption='[[6peb]], [[Resolution|resolution]] 2.46Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6peb]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PEB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PEB FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OE4:N-{4-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide'>OE4</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6atb|6atb]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nicotinamide_phosphoribosyltransferase Nicotinamide phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.12 2.4.2.12] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6peb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6peb OCA], [http://pdbe.org/6peb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6peb RCSB], [http://www.ebi.ac.uk/pdbsum/6peb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6peb ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/NAMPT_HUMAN NAMPT_HUMAN]] Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Small molecules that inhibit the metabolic enzyme NAMPT have emerged as potential therapeutics in oncology. As part of our effort in this area, we took a scaffold morphing approach and identified 3-pyridyl azetidine ureas as a potent NAMPT inhibiting motif. We explored the SAR of this series, including 5 and 6 amino pyridines, using a convergent synthetic strategy. This lead optimization campaign yielded multiple compounds with excellent in vitro potency and good ADME properties that culminated in compound 27. | |||
Scaffold Morphing Identifies 3-Pyridyl Azetidine Ureas as Inhibitors of Nicotinamide Phosphoribosyltransferase (NAMPT).,Palacios DS, Meredith EL, Kawanami T, Adams CM, Chen X, Darsigny V, Palermo M, Baird D, George EL, Guy C, Hewett J, Tierney L, Thigale S, Wang L, Weihofen WA ACS Med Chem Lett. 2019 Oct 10;10(11):1524-1529. doi:, 10.1021/acsmedchemlett.9b00325. eCollection 2019 Nov 14. PMID:31749905<ref>PMID:31749905</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6peb" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Nicotinamide phosphoribosyltransferase]] | |||
[[Category: Weihofen, W A]] | |||
[[Category: Transferase]] | |||
Revision as of 11:12, 4 December 2019
Crystal Structure of human NAMPT in complex with NVP-LTM976Crystal Structure of human NAMPT in complex with NVP-LTM976
Structural highlights
Function[NAMPT_HUMAN] Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway (By similarity). Publication Abstract from PubMedSmall molecules that inhibit the metabolic enzyme NAMPT have emerged as potential therapeutics in oncology. As part of our effort in this area, we took a scaffold morphing approach and identified 3-pyridyl azetidine ureas as a potent NAMPT inhibiting motif. We explored the SAR of this series, including 5 and 6 amino pyridines, using a convergent synthetic strategy. This lead optimization campaign yielded multiple compounds with excellent in vitro potency and good ADME properties that culminated in compound 27. Scaffold Morphing Identifies 3-Pyridyl Azetidine Ureas as Inhibitors of Nicotinamide Phosphoribosyltransferase (NAMPT).,Palacios DS, Meredith EL, Kawanami T, Adams CM, Chen X, Darsigny V, Palermo M, Baird D, George EL, Guy C, Hewett J, Tierney L, Thigale S, Wang L, Weihofen WA ACS Med Chem Lett. 2019 Oct 10;10(11):1524-1529. doi:, 10.1021/acsmedchemlett.9b00325. eCollection 2019 Nov 14. PMID:31749905[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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