8se6
From Proteopedia
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<table><tr><td colspan='2'>[[8se6]] 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=8SE6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SE6 FirstGlance]. <br> | <table><tr><td colspan='2'>[[8se6]] 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=8SE6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SE6 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]] 1.36Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.36Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=ZWA:N-[( | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=ZWA:~{N}-[(1~{S})-2-(dimethylamino)-2-oxidanylidene-1-[3-[3-[2,2,2-tris(fluoranyl)ethyl]azetidin-1-yl]phenyl]ethyl]-2-[4-(trifluoromethyl)phenyl]benzamide'>ZWA</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=8se6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8se6 OCA], [https://pdbe.org/8se6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8se6 RCSB], [https://www.ebi.ac.uk/pdbsum/8se6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8se6 ProSAT]</span></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=8se6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8se6 OCA], [https://pdbe.org/8se6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8se6 RCSB], [https://www.ebi.ac.uk/pdbsum/8se6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8se6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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Natural killer group 2D (NKG2D) is a homodimeric activating immunoreceptor whose function is to detect and eliminate compromised cells upon binding to the NKG2D ligands (NKG2DL) major histocompatibility complex (MHC) molecules class I-related chain A (MICA) and B (MICB) and UL16 binding proteins (ULBP1-6). While typically present at low levels in healthy cells and tissue, NKG2DL expression can be induced by viral infection, cellular stress or transformation. Aberrant activity along the NKG2D/NKG2DL axis has been associated with autoimmune diseases due to the increased expression of NKG2D ligands in human disease tissue, making NKG2D inhibitors an attractive target for immunomodulation. Herein we describe the discovery and optimization of small molecule PPI (protein-protein interaction) inhibitors of NKG2D/NKG2DL. Rapid SAR was guided by structure-based drug design and accomplished by iterative singleton and parallel medicinal chemistry synthesis. These efforts resulted in the identification of several potent analogs (14, 21, 30, 45) with functional activity and improved LLE. | Natural killer group 2D (NKG2D) is a homodimeric activating immunoreceptor whose function is to detect and eliminate compromised cells upon binding to the NKG2D ligands (NKG2DL) major histocompatibility complex (MHC) molecules class I-related chain A (MICA) and B (MICB) and UL16 binding proteins (ULBP1-6). While typically present at low levels in healthy cells and tissue, NKG2DL expression can be induced by viral infection, cellular stress or transformation. Aberrant activity along the NKG2D/NKG2DL axis has been associated with autoimmune diseases due to the increased expression of NKG2D ligands in human disease tissue, making NKG2D inhibitors an attractive target for immunomodulation. Herein we describe the discovery and optimization of small molecule PPI (protein-protein interaction) inhibitors of NKG2D/NKG2DL. Rapid SAR was guided by structure-based drug design and accomplished by iterative singleton and parallel medicinal chemistry synthesis. These efforts resulted in the identification of several potent analogs (14, 21, 30, 45) with functional activity and improved LLE. | ||
| - | Development of small molecule inhibitors of natural killer group 2D receptor (NKG2D).,Wang J, Nakafuku KM, Ziff J, Gelin CF, Gholami H, Thompson AA, Karpowich NK, Limon L, Coate HR, Damm-Ganamet KL, Shih AY, Grant JC, Cote M, Mak PA, Pascual HA, Rives ML, Edwards JP, Venable JD, Venkatesan H, Shi Z, Allen SJ, Sharma S, Kung PP, Shireman BT Bioorg Med Chem Lett. 2023 | + | Development of small molecule inhibitors of natural killer group 2D receptor (NKG2D).,Wang J, Nakafuku KM, Ziff J, Gelin CF, Gholami H, Thompson AA, Karpowich NK, Limon L, Coate HR, Damm-Ganamet KL, Shih AY, Grant JC, Cote M, Mak PA, Pascual HA, Rives ML, Edwards JP, Venable JD, Venkatesan H, Shi Z, Allen SJ, Sharma S, Kung PP, Shireman BT Bioorg Med Chem Lett. 2023 Nov 15;96:129492. doi: 10.1016/j.bmcl.2023.129492. , Epub 2023 Sep 29. PMID:37778428<ref>PMID:37778428</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
NKG2D complexed with inhibitor 36
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