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[[Image: | ==4-Methylpteridineones as Orally Active and Selective PI3K/mTOR Dual Inhibitors== | ||
<StructureSection load='3oaw' size='340' side='right' caption='[[3oaw]], [[Resolution|resolution]] 2.75Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3oaw]] is a 1 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=3OAW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OAW FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OAW:2-AMINO-4-METHYL-8-(1-METHYLETHYL)-6-(1H-PYRAZOL-4-YL)PTERIDIN-7(8H)-ONE'>OAW</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ml9|3ml9]], [[3ml8|3ml8]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PIK3CG ([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/Phosphatidylinositol-4,5-bisphosphate_3-kinase Phosphatidylinositol-4,5-bisphosphate 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.153 2.7.1.153] </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=3oaw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oaw OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3oaw RCSB], [http://www.ebi.ac.uk/pdbsum/3oaw PDBsum]</span></td></tr> | |||
</table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/oa/3oaw_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Pteridinones were designed based on a non-selective kinase template. Because of the uniqueness of the PI3K and mTOR binding pockets, a methyl group was introduced to C-4 position of the peteridinone core to give compounds with excellent selectivity for PI3K and mTOR. This series of compounds were further optimized to improve their potency against PI3Kalpha and mTOR. Finally, orally active compounds with improved solubility and robust in vivo efficacy in tumor growth inhibition were identified as well. | |||
4-Methylpteridinones as orally active and selective PI3K/mTOR dual inhibitors.,Liu KK, Bagrodia S, Bailey S, Cheng H, Chen H, Gao L, Greasley S, Hoffman JE, Hu Q, Johnson TO, Knighton D, Liu Z, Marx MA, Nambu MD, Ninkovic S, Pascual B, Rafidi K, Rodgers CM, Smith GL, Sun S, Wang H, Yang A, Yuan J, Zou A Bioorg Med Chem Lett. 2010 Oct 15;20(20):6096-9. Epub 2010 Aug 14. PMID:20817449<ref>PMID:20817449</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Phosphoinositide 3-Kinases|Phosphoinositide 3-Kinases]] | *[[Phosphoinositide 3-Kinases|Phosphoinositide 3-Kinases]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]] | [[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]] | ||
[[Category: Greasley, S E | [[Category: Greasley, S E]] | ||
[[Category: Knighton, D R | [[Category: Knighton, D R]] | ||
[[Category: Rodgers, C M.L | [[Category: Rodgers, C M.L]] | ||
[[Category: Inhibition]] | [[Category: Inhibition]] | ||
[[Category: Inhibitor complex | [[Category: Inhibitor complex]] | ||
[[Category: Phosphoinositide kinase]] | [[Category: Phosphoinositide kinase]] | ||
[[Category: Transferase-transferase]] | [[Category: Transferase-transferase]] | ||
[[Category: Transferase-transferase inhibitor complex]] | [[Category: Transferase-transferase inhibitor complex]] | ||
Revision as of 15:46, 9 December 2014
4-Methylpteridineones as Orally Active and Selective PI3K/mTOR Dual Inhibitors4-Methylpteridineones as Orally Active and Selective PI3K/mTOR Dual Inhibitors
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPteridinones were designed based on a non-selective kinase template. Because of the uniqueness of the PI3K and mTOR binding pockets, a methyl group was introduced to C-4 position of the peteridinone core to give compounds with excellent selectivity for PI3K and mTOR. This series of compounds were further optimized to improve their potency against PI3Kalpha and mTOR. Finally, orally active compounds with improved solubility and robust in vivo efficacy in tumor growth inhibition were identified as well. 4-Methylpteridinones as orally active and selective PI3K/mTOR dual inhibitors.,Liu KK, Bagrodia S, Bailey S, Cheng H, Chen H, Gao L, Greasley S, Hoffman JE, Hu Q, Johnson TO, Knighton D, Liu Z, Marx MA, Nambu MD, Ninkovic S, Pascual B, Rafidi K, Rodgers CM, Smith GL, Sun S, Wang H, Yang A, Yuan J, Zou A Bioorg Med Chem Lett. 2010 Oct 15;20(20):6096-9. Epub 2010 Aug 14. PMID:20817449[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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