6zac
From Proteopedia
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==PI3K Delta in complex with [(dimethylamino)methyldihydrobenzoxazin2methoxypyridinyl]methanesulfonamide== | ==PI3K Delta in complex with [(dimethylamino)methyldihydrobenzoxazin2methoxypyridinyl]methanesulfonamide== | ||
| - | <StructureSection load='6zac' size='340' side='right'caption='[[6zac]]' scene=''> | + | <StructureSection load='6zac' size='340' side='right'caption='[[6zac]], [[Resolution|resolution]] 2.15Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZAC OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZAC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZAC FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QDE:~{N}-[5-[6-[(dimethylamino)methyl]-2,3-dihydro-1,4-benzoxazin-4-yl]-2-methoxy-pyridin-3-yl]methanesulfonamide'>QDE</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=6zac FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zac OCA], [https://pdbe.org/6zac PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zac RCSB], [https://www.ebi.ac.uk/pdbsum/6zac PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zac ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A macrocyclization approach has been explored on a series of benzoxazine phosphoinositide 3-kinase delta inhibitors, resulting in compounds with improved potency, permeability, and in vivo clearance while maintaining good solubility. The thermodynamics of binding was explored via surface plasmon resonance, and the binding of lead macrocycle 19 was found to be almost exclusively entropically driven compared with progenitor 18, which demonstrated both enthalpic and entropic contributions. The pharmacokinetics of macrocycle 19 was also explored in vivo, where it showed reduced clearance when compared with the progenitor 18. This work adds to the growing body of evidence that macrocyclization could provide an alternative and complementary approach to the design of small-molecule inhibitors, with the potential to deliver differentiated properties. | ||
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| + | Design and Development of a Macrocyclic Series Targeting Phosphoinositide 3-Kinase delta.,Spencer JA, Baldwin IR, Barton N, Chung CW, Convery MA, Edwards CD, Jamieson C, Mallett DN, Rowedder JE, Rowland P, Thomas DA, Hardy CJ ACS Med Chem Lett. 2020 Jun 3;11(7):1386-1391. doi:, 10.1021/acsmedchemlett.0c00061. eCollection 2020 Jul 9. PMID:32676144<ref>PMID:32676144</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6zac" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Phosphoinositide 3-kinase 3D structures|Phosphoinositide 3-kinase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
PI3K Delta in complex with [(dimethylamino)methyldihydrobenzoxazin2methoxypyridinyl]methanesulfonamide
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