4kfn - Revision history

OCA at 12:12, 1 March 2024

OCA — Fri, 01 Mar 2024 12:12:18 GMT

←Older revision		Revision as of 12:12, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4kfn]] 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=4KFN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KFN FirstGlance]. <br>		<table><tr><td colspan='2'>[[4kfn]] 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=4KFN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KFN FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1QR:N-[4-(PIPERIDIN-1-YLSULFONYL)BENZYL]-1H-PYRROLO[3,2-C]PYRIDINE-2-CARBOXAMIDE'>1QR</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.6Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1QR:N-[4-(PIPERIDIN-1-YLSULFONYL)BENZYL]-1H-PYRROLO[3,2-C]PYRIDINE-2-CARBOXAMIDE'>1QR</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=4kfn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kfn OCA], [https://pdbe.org/4kfn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kfn RCSB], [https://www.ebi.ac.uk/pdbsum/4kfn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kfn ProSAT]</span></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=4kfn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kfn OCA], [https://pdbe.org/4kfn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kfn RCSB], [https://www.ebi.ac.uk/pdbsum/4kfn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kfn ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://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).		[https://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 ==
-	Nicotinamide phosphoribosyltransferase (Nampt) is a promising anticancer target. Virtual screening identified a thiourea analog, compound 5, as a novel highly potent Nampt inhibitor. Guided by the co-crystal structure of 5, SAR exploration revealed that the corresponding urea compound 7 exhibited similar potency with an improved solubility profile. These studies also indicated that a 3-pyridyl group was the preferred substituent at one inhibitor terminus and also identified a urea moiety as the optimal linker to the remainder of the inhibitor structure. Further SAR optimization of the other inhibitor terminus ultimately yielded compound 50 as a urea-containing Nampt inhibitor which exhibited excellent biochemical and cellular potency (enzyme IC50 = 0.007 uM; A2780 IC50 = 0.032 uM). Compound 50 also showed excellent in vivo antitumor efficacy when dosed orally in an A2780 ovarian tumor xenograft model (TGI of 97% was observed on day 17).
-
-	Structure-based Identification of Novel Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors.,Zheng X, Bauer P, Baumeister T, Buckmelter AJ, Caligiuri M, Clodfelter KH, Han B, Ho YC, Kley N, Lin J, Reynolds DJ, Sharma G, Smith CC, Wang Z, Dragovich PS, Oh A, Wang W, Zak M, Gunzner-Toste J, Zhao G, Yuen PW, Bair KW J Med Chem. 2013 Apr 25. PMID:23617784<ref>PMID:23617784</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4kfn" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Phosphoribosyltransferase 3D structures\|Phosphoribosyltransferase 3D structures]]		*[[Phosphoribosyltransferase 3D structures\|Phosphoribosyltransferase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 11:56, 30 November 2022

OCA — Wed, 30 Nov 2022 11:56:03 GMT

←Older revision		Revision as of 11:56, 30 November 2022
Line 1:		Line 1:

	==Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors==		==Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors==
-	<StructureSection load='4kfn' size='340' side='right' caption='[[4kfn]], [[Resolution\|resolution]] 1.60Å' scene=''>	+	<StructureSection load='4kfn' size='340' side='right'caption='[[4kfn]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4kfn]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KFN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4KFN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4kfn]] 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=4KFN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KFN FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1QR:N-[4-(PIPERIDIN-1-YLSULFONYL)BENZYL]-1H-PYRROLO[3,2-C]PYRIDINE-2-CARBOXAMIDE'>1QR</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1QR:N-[4-(PIPERIDIN-1-YLSULFONYL)BENZYL]-1H-PYRROLO[3,2-C]PYRIDINE-2-CARBOXAMIDE'>1QR</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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">[[4jr5\|4jr5]], [[4kfo\|4kfo]]</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=4kfn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kfn OCA], [https://pdbe.org/4kfn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kfn RCSB], [https://www.ebi.ac.uk/pdbsum/4kfn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kfn ProSAT]</span></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 HUMAN])</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=4kfn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kfn OCA], [~~http~~://pdbe.org/4kfn PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4kfn RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4kfn PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4kfn ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== 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).	+	[https://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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 20:

	==See Also==		==See Also==
-	*[[Phosphoribosyltransferase\|Phosphoribosyltransferase]]	+	*[[Phosphoribosyltransferase 3D structures\|Phosphoribosyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Nicotinamide phosphoribosyltransferase~~]]	+	[[Category: Large Structures]]
-	[[Category: Bair~~, K W~~]]	+	[[Category: Bair KW]]
-	[[Category: Bauer, P]]	+	[[Category: Bauer P]]
-	[[Category: Baumeister, T]]	+	[[Category: Baumeister T]]
-	~~[[Category: Brien, T O~~]]	+	[[Category: Buckmelter AJ]]
-	[[Category: Buckmelter~~, A J~~]]	+	[[Category: Caligiuri M]]
-	[[Category: Caligiuri, M]]	+	[[Category: Clodfelter KH]]
-	[[Category: Clodfelter~~, K H~~]]	+	[[Category: Dragovich PS]]
-	[[Category: Dragovich~~, P S~~]]	+	[[Category: Gunzner-Toste J]]
-	[[Category: Gunzner-Toste, J]]	+	[[Category: Han B]]
-	[[Category: Han, B]]	+	[[Category: Ho Y]]
-	[[Category: Ho, Y]]	+	[[Category: Kley N]]
-	[[Category: Kley, N]]	+	[[Category: Liederer BM]]
-	[[Category: Liederer~~, B M~~]]	+	[[Category: Lin J]]
-	[[Category: Lin, J]]	+	[[Category: Ly J]]
-	[[Category: Ly, J]]	+	[[Category: O'Brien T]]
-	[[Category: Oh, A]]	+	[[Category: Oh A]]
-	[[Category: Reynolds~~, D J~~]]	+	[[Category: Reynolds DJ]]
-	[[Category: Sharma, G]]	+	[[Category: Sharma G]]
-	[[Category: Smith~~, C C~~]]	+	[[Category: Smith CC]]
-	[[Category: Wang, L]]	+	[[Category: Wang L]]
-	[[Category: Wang, W]]	+	[[Category: Wang W]]
-	[[Category: Wang, Z]]	+	[[Category: Wang Z]]
-	[[Category: Xiao, Y]]	+	[[Category: Xiao Y]]
-	[[Category: Yuen, P]]	+	[[Category: Yuen P]]
-	[[Category: Zak, M]]	+	[[Category: Zak M]]
-	[[Category: Zhao, G]]	+	[[Category: Zhao G]]
-	[[Category: Zheng, X]]	+	[[Category: Zheng X]]
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 17:01, 4 August 2016

OCA — Thu, 04 Aug 2016 17:01:09 GMT

←Older revision		Revision as of 17:01, 4 August 2016
Line 1:		Line 1:
		+
	==Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors==		==Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors==
	<StructureSection load='4kfn' size='340' side='right' caption='[[4kfn]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='4kfn' size='340' side='right' caption='[[4kfn]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4kfn]] 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=4KFN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KFN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4kfn]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KFN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KFN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1QR:N-[4-(PIPERIDIN-1-YLSULFONYL)BENZYL]-1H-PYRROLO[3,2-C]PYRIDINE-2-CARBOXAMIDE'>1QR</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1QR:N-[4-(PIPERIDIN-1-YLSULFONYL)BENZYL]-1H-PYRROLO[3,2-C]PYRIDINE-2-CARBOXAMIDE'>1QR</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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">[[4jr5\|4jr5]], [[4kfo\|4kfo]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4jr5\|4jr5]], [[4kfo\|4kfo]]</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='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 HUMAN])</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='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=4kfn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kfn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kfn RCSB], [http://www.ebi.ac.uk/pdbsum/4kfn PDBsum]</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=4kfn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kfn OCA], [http://pdbe.org/4kfn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kfn RCSB], [http://www.ebi.ac.uk/pdbsum/4kfn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kfn ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4kfn" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Nicotinamide phosphoribosyltransferase]]		[[Category: Nicotinamide phosphoribosyltransferase]]
	[[Category: Bair, K W]]		[[Category: Bair, K W]]

OCA at 11:12, 25 December 2014

OCA — Thu, 25 Dec 2014 11:12:15 GMT

←Older revision		Revision as of 11:12, 25 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4kfn\| PDB=4kfn \| SCENE= }}~~	+	==Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors==
-	===Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors===	+	<StructureSection load='4kfn' size='340' side='right' caption='[[4kfn]], [[Resolution\|resolution]] 1.60Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23617784}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4kfn]] 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=4KFN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KFN FirstGlance]. <br>
-	==Function==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1QR:N-[4-(PIPERIDIN-1-YLSULFONYL)BENZYL]-1H-PYRROLO[3,2-C]PYRIDINE-2-CARBOXAMIDE'>1QR</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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">[[4jr5\|4jr5]], [[4kfo\|4kfo]]</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=4kfn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kfn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kfn RCSB], [http://www.ebi.ac.uk/pdbsum/4kfn 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 ==
		+	Nicotinamide phosphoribosyltransferase (Nampt) is a promising anticancer target. Virtual screening identified a thiourea analog, compound 5, as a novel highly potent Nampt inhibitor. Guided by the co-crystal structure of 5, SAR exploration revealed that the corresponding urea compound 7 exhibited similar potency with an improved solubility profile. These studies also indicated that a 3-pyridyl group was the preferred substituent at one inhibitor terminus and also identified a urea moiety as the optimal linker to the remainder of the inhibitor structure. Further SAR optimization of the other inhibitor terminus ultimately yielded compound 50 as a urea-containing Nampt inhibitor which exhibited excellent biochemical and cellular potency (enzyme IC50 = 0.007 uM; A2780 IC50 = 0.032 uM). Compound 50 also showed excellent in vivo antitumor efficacy when dosed orally in an A2780 ovarian tumor xenograft model (TGI of 97% was observed on day 17).
		+
		+	Structure-based Identification of Novel Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors.,Zheng X, Bauer P, Baumeister T, Buckmelter AJ, Caligiuri M, Clodfelter KH, Han B, Ho YC, Kley N, Lin J, Reynolds DJ, Sharma G, Smith CC, Wang Z, Dragovich PS, Oh A, Wang W, Zak M, Gunzner-Toste J, Zhao G, Yuen PW, Bair KW J Med Chem. 2013 Apr 25. PMID:23617784<ref>PMID:23617784</ref>

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4kfn]] 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=4KFN OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:023617784</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[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: Bauer, P.]]	+	[[Category: Bauer, P]]
-	[[Category: Baumeister, T.]]	+	[[Category: Baumeister, T]]
-	[[Category: Brien, T O.]]	+	[[Category: Brien, T O]]
-	[[Category: Buckmelter, A J.]]	+	[[Category: Buckmelter, A J]]
-	[[Category: Caligiuri, M.]]	+	[[Category: Caligiuri, M]]
-	[[Category: Clodfelter, K H.]]	+	[[Category: Clodfelter, K H]]
-	[[Category: Dragovich, P S.]]	+	[[Category: Dragovich, P S]]
-	[[Category: Gunzner-Toste, J.]]	+	[[Category: Gunzner-Toste, J]]
-	[[Category: Han, B.]]	+	[[Category: Han, B]]
-	[[Category: Ho, Y.]]	+	[[Category: Ho, Y]]
-	[[Category: Kley, N.]]	+	[[Category: Kley, N]]
-	[[Category: Liederer, B M.]]	+	[[Category: Liederer, B M]]
-	[[Category: Lin, J.]]	+	[[Category: Lin, J]]
-	[[Category: Ly, J.]]	+	[[Category: Ly, J]]
-	[[Category: Oh, A.]]	+	[[Category: Oh, A]]
-	[[Category: Reynolds, D J.]]	+	[[Category: Reynolds, D J]]
-	[[Category: Sharma, G.]]	+	[[Category: Sharma, G]]
-	[[Category: Smith, C C.]]	+	[[Category: Smith, C C]]
-	[[Category: Wang, L.]]	+	[[Category: Wang, L]]
-	[[Category: Wang, W.]]	+	[[Category: Wang, W]]
-	[[Category: Wang, Z.]]	+	[[Category: Wang, Z]]
-	[[Category: Xiao, Y.]]	+	[[Category: Xiao, Y]]
-	[[Category: Yuen, P.]]	+	[[Category: Yuen, P]]
-	[[Category: Zak, M.]]	+	[[Category: Zak, M]]
-	[[Category: Zhao, G.]]	+	[[Category: Zhao, G]]
-	[[Category: Zheng, X.]]	+	[[Category: Zheng, X]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 07:20, 30 June 2013

OCA — Sun, 30 Jun 2013 07:20:40 GMT

←Older revision		Revision as of 07:20, 30 June 2013
Line 8:		Line 8:
	==About this Structure==		==About this Structure==
	[[4kfn]] 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=4KFN OCA].		[[4kfn]] 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=4KFN OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:023617784</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Nicotinamide phosphoribosyltransferase]]		[[Category: Nicotinamide phosphoribosyltransferase]]

OCA: Protected "4kfn" [edit=sysop:move=sysop]

OCA — Wed, 08 May 2013 07:44:00 GMT

Protected "4kfn" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:44, 8 May 2013

OCA: New page: {{STRUCTURE_4kfn| PDB=4kfn | SCENE= }} ===Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors=== {{ABSTRACT_PUBMED_23617784}}...

OCA — Wed, 08 May 2013 07:43:57 GMT

New page: {{STRUCTURE_4kfn| PDB=4kfn | SCENE= }} ===Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors=== {{ABSTRACT_PUBMED_23617784}}...

New page

{{STRUCTURE_4kfn| PDB=4kfn | SCENE= }}
===Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors===
{{ABSTRACT_PUBMED_23617784}}

==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).

==About this Structure==
[[4kfn]] 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=4KFN OCA].
[[Category: Homo sapiens]]
[[Category: Nicotinamide phosphoribosyltransferase]]
[[Category: Bair, K W.]]
[[Category: Bauer, P.]]
[[Category: Baumeister, T.]]
[[Category: Brien, T O.]]
[[Category: Buckmelter, A J.]]
[[Category: Caligiuri, M.]]
[[Category: Clodfelter, K H.]]
[[Category: Dragovich, P S.]]
[[Category: Gunzner-Toste, J.]]
[[Category: Han, B.]]
[[Category: Ho, Y.]]
[[Category: Kley, N.]]
[[Category: Liederer, B M.]]
[[Category: Lin, J.]]
[[Category: Ly, J.]]
[[Category: Oh, A.]]
[[Category: Reynolds, D J.]]
[[Category: Sharma, G.]]
[[Category: Smith, C C.]]
[[Category: Wang, L.]]
[[Category: Wang, W.]]
[[Category: Wang, Z.]]
[[Category: Xiao, Y.]]
[[Category: Yuen, P.]]
[[Category: Zak, M.]]
[[Category: Zhao, G.]]
[[Category: Zheng, X.]]
[[Category: Transferase-transferase inhibitor complex]]