7m41
From Proteopedia
(Difference between revisions)
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==Structure of TIM-3 in complex with N-(4-(8-chloro-2-methyl-5-oxo-5,6-dihydro-[1,2,4]traizolo[1,5-c]quinazolin-9-yl)-3-methylphenyl)-1H-imidazole-2-sulfonamide (compound 38)== | ==Structure of TIM-3 in complex with N-(4-(8-chloro-2-methyl-5-oxo-5,6-dihydro-[1,2,4]traizolo[1,5-c]quinazolin-9-yl)-3-methylphenyl)-1H-imidazole-2-sulfonamide (compound 38)== | ||
- | <StructureSection load='7m41' size='340' side='right'caption='[[7m41]]' scene=''> | + | <StructureSection load='7m41' size='340' side='right'caption='[[7m41]], [[Resolution|resolution]] 1.79Å' 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=7M41 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M41 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7m41]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7M41 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M41 FirstGlance]. <br> |
- | </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=7m41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m41 OCA], [https://pdbe.org/7m41 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m41 RCSB], [https://www.ebi.ac.uk/pdbsum/7m41 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m41 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=YQG:N-{4-[(4S,10aP)-8-chloro-2-methyl-5-oxo-5,6-dihydro[1,2,4]triazolo[1,5-c]quinazolin-9-yl]-3-methylphenyl}-1H-imidazole-2-sulfonamide'>YQG</scene></td></tr> |
+ | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7m3y|7m3y]], [[7m3z|7m3z]]</div></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=7m41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m41 OCA], [https://pdbe.org/7m41 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m41 RCSB], [https://www.ebi.ac.uk/pdbsum/7m41 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m41 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
+ | == Function == | ||
+ | [[https://www.uniprot.org/uniprot/HAVR2_HUMAN HAVR2_HUMAN]] Regulates macrophage activation. Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance. May be also involved in T-cell homing. Receptor for LGALS9.<ref>PMID:14556005</ref> <ref>PMID:16286920</ref> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3; HAVCR2) has emerged as an attractive immune checkpoint target for cancer immunotherapy. TIM-3 is a negative regulator of the systemic immune response to cancer and is expressed on several dysfunctional, or exhausted, immune cell subsets. Upregulation of TIM-3 is associated with tumor progression, poor survival rates, and acquired resistance to antibody-based immunotherapies in the clinic. Despite the potential advantages of small-molecule inhibitors over antibodies, the discovery of small-molecule inhibitors has lagged behind that of antibody therapeutics. Here, we describe the discovery of high-affinity small-molecule ligands for TIM-3 through an NMR-based fragment screen and structure-based lead optimization. These compounds represent useful tools to further study the biology of TIM-3 immune modulation in cancer and serve as a potentially useful starting point toward the discovery of TIM-3-targeted therapeutics. | ||
+ | |||
+ | Fragment-Based Discovery of Small Molecules Bound to T-Cell Immunoglobulin and Mucin Domain-Containing Molecule 3 (TIM-3).,Rietz TA, Teuscher KB, Mills JJ, Gogliotti RD, Lepovitz LT, Scaggs WR, Yoshida K, Luong K, Lee T, Fesik SW J Med Chem. 2021 Oct 1. doi: 10.1021/acs.jmedchem.1c01336. PMID:34597046<ref>PMID:34597046</ref> | ||
+ | |||
+ | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
+ | </div> | ||
+ | <div class="pdbe-citations 7m41" style="background-color:#fffaf0;"></div> | ||
+ | == References == | ||
+ | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
- | [[Category: Rietz | + | [[Category: Rietz, T A]] |
+ | [[Category: Igv]] | ||
+ | [[Category: Immune system]] |
Revision as of 15:51, 27 October 2021
Structure of TIM-3 in complex with N-(4-(8-chloro-2-methyl-5-oxo-5,6-dihydro-[1,2,4]traizolo[1,5-c]quinazolin-9-yl)-3-methylphenyl)-1H-imidazole-2-sulfonamide (compound 38)
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