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==The 1.9A crystal structure of humanized Xenopus MDM2 with RO5313109 - a pyrrolidine MDM2 inhibitor== | |||
<StructureSection load='4jrg' size='340' side='right' caption='[[4jrg]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4jrg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/African_clawed_frog African clawed frog]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JRG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JRG FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=I09:(3R,4R,5S)-3-(3-CHLOROPHENYL)-4-(4-CHLOROPHENYL)-4-CYANO-N-[(3S)-3,4-DIHYDROXYBUTYL]-5-(2,2-DIMETHYLPROPYL)-D-PROLINAMIDE'>I09</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ipf|4ipf]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mdm2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog])</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=4jrg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jrg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jrg RCSB], [http://www.ebi.ac.uk/pdbsum/4jrg PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/MDM2_XENLA MDM2_XENLA]] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Restoration of p53 activity by inhibition of the p53-MDM2 interaction has been considered an attractive approach for cancer treatment. However, the hydrophobic protein-protein interaction surface represents a significant challenge for the development of small-molecule inhibitors with desirable pharmacological profiles. RG7112 was the first small-molecule p53-MDM2 inhibitor in clinical development. Here, we report the discovery and characterization of a second generation clinical MDM2 inhibitor, RG7388, with superior potency and selectivity. | |||
Discovery of RG7388, a Potent and Selective p53-MDM2 Inhibitor in Clinical Development.,Ding Q, Zhang Z, Liu JJ, Jiang N, Zhang J, Ross TM, Chu XJ, Bartkovitz D, Podlaski F, Janson C, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev LT, Graves B J Med Chem. 2013 Jul 16. PMID:23808545<ref>PMID:23808545</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== | ==See Also== | ||
*[[MDM2|MDM2]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: African clawed frog]] | [[Category: African clawed frog]] | ||
[[Category: Graves, B J | [[Category: Graves, B J]] | ||
[[Category: Janson, C A | [[Category: Janson, C A]] | ||
[[Category: Lukacs, C | [[Category: Lukacs, C]] | ||
[[Category: E3 ubiquitin ligase]] | [[Category: E3 ubiquitin ligase]] | ||
[[Category: Ligase-ligase inhibitor complex]] | [[Category: Ligase-ligase inhibitor complex]] | ||
Revision as of 05:36, 25 December 2014
The 1.9A crystal structure of humanized Xenopus MDM2 with RO5313109 - a pyrrolidine MDM2 inhibitorThe 1.9A crystal structure of humanized Xenopus MDM2 with RO5313109 - a pyrrolidine MDM2 inhibitor
Structural highlights
Function[MDM2_XENLA] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome (By similarity). Publication Abstract from PubMedRestoration of p53 activity by inhibition of the p53-MDM2 interaction has been considered an attractive approach for cancer treatment. However, the hydrophobic protein-protein interaction surface represents a significant challenge for the development of small-molecule inhibitors with desirable pharmacological profiles. RG7112 was the first small-molecule p53-MDM2 inhibitor in clinical development. Here, we report the discovery and characterization of a second generation clinical MDM2 inhibitor, RG7388, with superior potency and selectivity. Discovery of RG7388, a Potent and Selective p53-MDM2 Inhibitor in Clinical Development.,Ding Q, Zhang Z, Liu JJ, Jiang N, Zhang J, Ross TM, Chu XJ, Bartkovitz D, Podlaski F, Janson C, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev LT, Graves B J Med Chem. 2013 Jul 16. PMID:23808545[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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