8s9h
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of monkey TLR7 ectodomain with compound 14== | |
| + | <StructureSection load='8s9h' size='340' side='right'caption='[[8s9h]], [[Resolution|resolution]] 2.44Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8s9h]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Macaca_mulatta Macaca mulatta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8S9H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8S9H 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]] 2.437Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZWV:(3S)-3-{[5-amino-1-({3-methoxy-5-[1-(oxan-4-yl)piperidin-4-yl]pyridin-2-yl}methyl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl]amino}hexan-1-ol'>ZWV</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=8s9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8s9h OCA], [https://pdbe.org/8s9h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8s9h RCSB], [https://www.ebi.ac.uk/pdbsum/8s9h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8s9h ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/B3Y653_MACMU B3Y653_MACMU] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Small molecule toll-like receptor (TLR) 7 agonists have gathered considerable interest as promising therapeutic agents for applications in cancer immunotherapy. Herein, we describe the development and optimization of a series of novel TLR7 agonists through systematic structure-activity relationship studies focusing on modification of the phenylpiperidine side chain. Additional refinement of ADME properties culminated in the discovery of compound 14, which displayed nanomolar reporter assay activity and favorable drug-like properties. Compound 14 demonstrated excellent in vivo pharmacokinetic/pharmacodynamic profiles and synergistic antitumor activity when administered in combination with aPD1 antibody, suggesting opportunities of employing 14 in immuno-oncology therapies with immune checkpoint blockade agents. | ||
| - | + | Identification and Optimization of Small Molecule Pyrazolopyrimidine TLR7 Agonists for Applications in Immuno-oncology.,He L, Zhang MY, Cox M, Zhang Q, Donnell AF, Zhang Y, Tarby C, Gill P, Subbaiah MAM, Ramar T, Reddy M, Puttapaka V, Li YX, Sivaprakasam P, Critton D, Mulligan D, Xie C, Ramakrishnan R, Nagar J, Dudhgaonkar S, Murtaza A, Oderinde MS, Schieven GL, Mathur A, Gavai AV, Vite G, Gangwar S, Poudel YB ACS Med Chem Lett. 2024 Jan 9;15(2):189-196. doi: 10.1021/acsmedchemlett.3c00456. , eCollection 2024 Feb 8. PMID:38352849<ref>PMID:38352849</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8s9h" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Macaca mulatta]] | ||
| + | [[Category: Critton DA]] | ||
Current revision
Crystal structure of monkey TLR7 ectodomain with compound 14
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