View source for 7bea


==Structure of human Programmed cell death 1 ligand 1 (PD-L1) with inhibitor==
<StructureSection load='7bea' size='340' side='right'caption='[[7bea]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7bea]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BEA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BEA 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]] 2.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TK2:2-(aminomethyl)-6-[(2-methyl-3-phenyl-phenyl)methoxy]-~{N}-(2-phenylethyl)imidazo[1,2-a]pyridin-3-amine'>TK2</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=7bea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bea OCA], [https://pdbe.org/7bea PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bea RCSB], [https://www.ebi.ac.uk/pdbsum/7bea PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bea ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PD1L1_HUMAN PD1L1_HUMAN] Involved in the costimulatory signal, essential for T-cell proliferation and production of IL10 and IFNG, in an IL2-dependent and a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation and cytokine production.<ref>PMID:10581077</ref> <ref>PMID:11015443</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The PD-1/PD-L1 axis has proven to be a highly efficacious target for cancer immune checkpoint therapy with several approved antibodies. Also, small molecules based on a biphenyl core can antagonize PD-1/PD-L1, leading to the in vitro formation of PD-L1 dimers. However, their development remains challenging, as we do not yet fully understand their mode of action. In this work, we designed a new scaffold based on our previously solved high-resolution structures of low-molecular-weight inhibitors bound to PD-L1. A small compound library was synthesized using the Groebke-Blackburn-Bienayme multicomponent reaction (GBB-3CR), resulting in the structure-activity relationship of imidazo[1,2-a]pyridine-based inhibitors. These inhibitors were tested for their biological activity using various biophysical assays giving potent candidates with low-micromolar PD-L1 affinities. An obtained PD-L1 cocrystal structure reveals the binding to PD-L1. Our results open the door to an interesting bioactive scaffold that could lead to a new class of PD-L1 antagonists.

Design, Synthesis, and Biological Evaluation of Imidazopyridines as PD-1/PD-L1 Antagonists.,Butera R, Wazynska M, Magiera-Mularz K, Plewka J, Musielak B, Surmiak E, Sala D, Kitel R, de Bruyn M, Nijman HW, Elsinga PH, Holak TA, Domling A ACS Med Chem Lett. 2021 Apr 28;12(5):768-773. doi:, 10.1021/acsmedchemlett.1c00033. eCollection 2021 May 13. PMID:34055224<ref>PMID:34055224</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7bea" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Butera R]]
[[Category: Domling A]]
[[Category: Holak T]]
[[Category: Magiera-Mularz K]]
[[Category: Wazynska M]]