View source for 8ttz


==Crystal structure of monkey TLR7 ectodomain with compound 20==
<StructureSection load='8ttz' size='340' side='right'caption='[[8ttz]], [[Resolution|resolution]] 3.14&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ttz]] 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=8TTZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TTZ 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]] 3.14&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=QCX:(3S)-3-({5-amino-1-[(2-methoxy-4-{[(oxan-4-yl)amino]methyl}phenyl)methyl]-1H-pyrazolo[4,3-d]pyrimidin-7-yl}amino)hexan-1-ol'>QCX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=8ttz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ttz OCA], [https://pdbe.org/8ttz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ttz RCSB], [https://www.ebi.ac.uk/pdbsum/8ttz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ttz ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We have designed and developed novel and selective TLR7 agonists that exhibited potent receptor activity in a cell-based reporter assay. In vitro, these agonists significantly induced secretion of cytokines IL-6, IL-1beta, IL-10, TNFa, IFNa, and IP-10 in human and mouse whole blood. Pharmacokinetic and pharmacodynamic studies in mice showed a significant secretion of IFNalpha and TNFalpha cytokines. When combined with aPD1 in a CT-26 tumor model, the lead compound showed strong synergistic antitumor activity with complete tumor regression in 8/10 mice dosed using the intravenous route. Structure-activity relationship studies enabled by structure-based designs of TLR7 agonists are disclosed.

Discovery of Novel TLR7 Agonists as Systemic Agent for Combination With aPD1 for Use in Immuno-oncology.,Poudel YB, He L, Cox M, Zhang Q, Johnson WL, Cong Q, Cheng H, Chowdari NS, Tarby C, Donnell AF, Broekema M, O'Malley DP, Zhang Y, A M Subbaiah M, Kumar BV, Subramani L, Wang B, Li YX, Sivaprakasam P, Critton D, Mulligan D, Sandhu B, Xie C, Ramakrishnan R, Nagar J, Dudhgaonkar S, Oderinde MS, Murtaza A, Schieven GL, Mathur A, Gavai AV, Vite G, Gangwar S ACS Med Chem Lett. 2024 Jan 8;15(2):181-188. doi: 10.1021/acsmedchemlett.3c00455. , eCollection 2024 Feb 8. PMID:38352830<ref>PMID:38352830</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ttz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Macaca mulatta]]
[[Category: Critton DA]]