4kfp
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | + | ==Identification of 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived Ureas as Potent Inhibitors of Human Nicotinamide Phosphoribosyltransferase (NAMPT)== | |
| - | + | <StructureSection load='4kfp' size='340' side='right' caption='[[4kfp]], [[Resolution|resolution]] 1.84Å' scene=''> | |
| - | { | + | == Structural highlights == |
| - | + | <table><tr><td colspan='2'>[[4kfp]] is a 2 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=4KFP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KFP FirstGlance]. <br> | |
| - | ==Function== | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1R7:N-(4-{[1-(TETRAHYDRO-2H-PYRAN-4-YL)PIPERIDIN-4-YL]SULFONYL}BENZYL)-2H-PYRROLO[3,4-C]PYRIDINE-2-CARBOXAMIDE'>1R7</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NAMPT, PBEF, PBEF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4kfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kfp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kfp RCSB], [http://www.ebi.ac.uk/pdbsum/4kfp PDBsum]</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). | [[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 == | ||
| + | Potent nicotinamide phosphoribosyltransferase (NAMPT) inhibitors containing 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived ureas were identified using structure-based design techniques. The new compounds displayed improved aqueous solubilities, determined using a high-throughput solubility assessment, relative to previously disclosed urea and amide-containing NAMPT inhibitors. An optimized 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived compound exhibited potent anti-NAMPT activity (18; BC NAMPT IC50=11nM; PC-3 antiproliferative IC50=36nM), satisfactory mouse PK properties, and was efficacious in a PC-3 mouse xenograft model. The crystal structure of another optimized compound (29; NAMPT IC50=10nM; A2780 antiproliferative IC50=7nM) in complex with the NAMPT protein was also determined. | ||
| + | |||
| + | Identification of 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived ureas as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT).,Dragovich PS, Bair KW, Baumeister T, Ho YC, Liederer BM, Liu X, Liu Y, O'Brien T, Oeh J, Sampath D, Skelton N, Wang L, Wang W, Wu H, Xiao Y, Yuen PW, Zak M, Zhang L, Zheng X Bioorg Med Chem Lett. 2013 Sep 1;23(17):4875-85. doi: 10.1016/j.bmcl.2013.06.090., Epub 2013 Jul 6. PMID:23899614<ref>PMID:23899614</ref> | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | == | + | ==See Also== |
| - | + | *[[Phosphoribosyltransferase|Phosphoribosyltransferase]] | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Nicotinamide phosphoribosyltransferase]] | [[Category: Nicotinamide phosphoribosyltransferase]] | ||
| - | [[Category: Bair, K W | + | [[Category: Bair, K W]] |
| - | [[Category: Baumeister, T | + | [[Category: Baumeister, T]] |
| - | [[Category: Brien, T O | + | [[Category: Brien, T O]] |
| - | [[Category: Dragovich, P S | + | [[Category: Dragovich, P S]] |
| - | [[Category: Ho, Y | + | [[Category: Ho, Y]] |
| - | [[Category: Liederer, B M | + | [[Category: Liederer, B M]] |
| - | [[Category: Liu, X | + | [[Category: Liu, X]] |
| - | [[Category: Oeh, J | + | [[Category: Oeh, J]] |
| - | [[Category: Sampath, D | + | [[Category: Sampath, D]] |
| - | [[Category: Skelton, N | + | [[Category: Skelton, N]] |
| - | [[Category: Wang, L | + | [[Category: Wang, L]] |
| - | [[Category: Wang, W | + | [[Category: Wang, W]] |
| - | [[Category: Wu, H | + | [[Category: Wu, H]] |
| - | [[Category: Xiao, Y | + | [[Category: Xiao, Y]] |
| - | [[Category: Yuen, P | + | [[Category: Yuen, P]] |
| - | [[Category: Zak, M | + | [[Category: Zak, M]] |
| - | [[Category: Zhang, L | + | [[Category: Zhang, L]] |
| - | [[Category: Zheng, X | + | [[Category: Zheng, X]] |
[[Category: Transferase-transferase inhibitor complex]] | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 22:00, 25 December 2014
Identification of 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived Ureas as Potent Inhibitors of Human Nicotinamide Phosphoribosyltransferase (NAMPT)
| |||||||||||
Categories: Homo sapiens | Nicotinamide phosphoribosyltransferase | Bair, K W | Baumeister, T | Brien, T O | Dragovich, P S | Ho, Y | Liederer, B M | Liu, X | Oeh, J | Sampath, D | Skelton, N | Wang, L | Wang, W | Wu, H | Xiao, Y | Yuen, P | Zak, M | Zhang, L | Zheng, X | Transferase-transferase inhibitor complex
