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The | ==Crystal structure of A2A adenosine receptor A2AR-bRIL in complex with Compound50== | ||
<StructureSection load='10kt' size='340' side='right'caption='[[10kt]], [[Resolution|resolution]] 2.59Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[10kt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=10KT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=10KT FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.59Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1C5S:2-[(3~{R},6~{S})-1-(1-ethylpyrazol-4-yl)-6-methyl-piperidin-3-yl]-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-5-amine'>A1C5S</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLB:(2S)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLB</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=10kt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=10kt OCA], [https://pdbe.org/10kt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=10kt RCSB], [https://www.ebi.ac.uk/pdbsum/10kt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=10kt ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/AA2AR_HUMAN AA2AR_HUMAN] Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Immune cells expressing the adenosine A(2A) receptor (A(2A)R) and A(2B) receptor (A(2B)R) present in an adenosine-rich tumor microenvironment have suppressed effector functions, such as proinflammatory cytokine release, antigen presentation, and others, making them inert to cancer cells. Simultaneous blockade of the downstream effects mediated by both receptor subtypes with a dual inhibitor has the potential to reverse adenosine-mediated suppression of tumor immune surveillance as either a single-agent treatment or in combination with other immunotherapy agents such as anti-PD-1/PD-L1 monoclonal antibodies. This publication describes the discovery and optimization of a novel series of potent and selective dual A(2A)R/A(2B)R antagonists, resulting in compound 46 (MK-1088) being identified for progression to human clinical studies. | |||
Discovery of MK-1088 as a Potent A(2A)/A(2B) Adenosine Receptor Dual-Antagonist for Cancer Immunotherapy.,Zhang Y, Hennessy E, Larsen MA, Hao J, Pan J, Mansoor UF, Sather A, Brill ZG, Rico L, Swaminathan U, Moreno J, Vara BA, Ranganath S, Palmieri A, Ogunbodede O, Barry ER, Hinton MC, Daublain P, Gupta P, Chatterjee M, Rottey S, Presland J, Hill AD, Dewey WJ, Schneider SE, Ciaccio PJ, Otte KM, Rindgen D, Tatosian D, Turnbull BWH, Silverman SM, Chobanian H, Krishnamurthy H, Pang L, Wnek R, Afshar R, Crowley S, Miller A, O'Neil J, Chrencik J, Plummer CW, Ali A, Cumming J, DeMong DE J Med Chem. 2026 May 14;69(9):10338-10359. doi: 10.1021/acs.jmedchem.5c03405. , Epub 2026 May 5. PMID:42084562<ref>PMID:42084562</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Krishnamurthy | <div class="pdbe-citations 10kt" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Krishnamurthy H]] | |||
Revision as of 11:21, 24 May 2026
Crystal structure of A2A adenosine receptor A2AR-bRIL in complex with Compound50
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