4jr5

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
{{STRUCTURE_4jr5| PDB=4jr5 | SCENE= }}
+
==Structure-based Identification of Ureas as Novel Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors==
-
===Structure-based Identification of Ureas as Novel Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors===
+
<StructureSection load='4jr5' size='340' side='right' caption='[[4jr5]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
-
{{ABSTRACT_PUBMED_23617784}}
+
== Structural highlights ==
-
 
+
<table><tr><td colspan='2'>[[4jr5]] 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=4JR5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JR5 FirstGlance]. <br>
-
==Function==
+
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1LS:1-[4-(PIPERIDIN-1-YLSULFONYL)PHENYL]-3-(PYRIDIN-3-YLMETHYL)THIOUREA'>1LS</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">[[4jnm|4jnm]], [[4kfn|4kfn]], [[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=4jr5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jr5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jr5 RCSB], [http://www.ebi.ac.uk/pdbsum/4jr5 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[4jr5]] 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=4JR5 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: 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: Lin, J.]]
+
[[Category: Lin, 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, W.]]
+
[[Category: Wang, W]]
-
[[Category: Wang, Z.]]
+
[[Category: Wang, Z]]
-
[[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]]

Revision as of 07:16, 25 December 2014

Structure-based Identification of Ureas as Novel Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors

4jr5, resolution 1.91Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4jr5"
Personal tools