8fp1
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8fp1]] is a 1 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=8FP1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FP1 FirstGlance]. <br> | <table><tr><td colspan='2'>[[8fp1]] is a 1 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=8FP1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FP1 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=XXF:(3P)-3-[6-chloro-4-(9-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile'>XXF</scene></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]] 1.85Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=XXF:(3P)-3-[6-chloro-4-(9-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzonitrile'>XXF</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=8fp1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fp1 OCA], [https://pdbe.org/8fp1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fp1 RCSB], [https://www.ebi.ac.uk/pdbsum/8fp1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fp1 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=8fp1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fp1 OCA], [https://pdbe.org/8fp1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fp1 RCSB], [https://www.ebi.ac.uk/pdbsum/8fp1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fp1 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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Immune activating agents represent a valuable class of therapeutics for the treatment of cancer. An area of active research is expanding the types of these therapeutics that are available to patients via targeting new biological mechanisms. Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of immune signaling and a target of high interest for the treatment of cancer. Herein, we present the discovery and optimization of novel amino-6-aryl pyrrolopyrimidine inhibitors of HPK1 starting from hits identified via virtual screening. Key components of this discovery effort were structure-based drug design aided by analyses of normalized B-factors and optimization of lipophilic efficiency. | Immune activating agents represent a valuable class of therapeutics for the treatment of cancer. An area of active research is expanding the types of these therapeutics that are available to patients via targeting new biological mechanisms. Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of immune signaling and a target of high interest for the treatment of cancer. Herein, we present the discovery and optimization of novel amino-6-aryl pyrrolopyrimidine inhibitors of HPK1 starting from hits identified via virtual screening. Key components of this discovery effort were structure-based drug design aided by analyses of normalized B-factors and optimization of lipophilic efficiency. | ||
| - | Design and Synthesis of Functionally Active 5-Amino-6-Aryl Pyrrolopyrimidine Inhibitors of Hematopoietic Progenitor Kinase 1.,Gallego RA, Bernier L, Chen H, Cho-Schultz S, Chung L, Collins M, Del Bel M, Elleraas J, Costa Jones C, Cronin CN, Edwards M, Fang X, Fisher T, He M, Hoffman J, Huo R, Jalaie M, Johnson E, Johnson TW, Kania RS, Kraus M, Lafontaine J, Le P, Liu T, Maestre M, Matthews J, McTigue M, Miller N, Mu Q, Qin X, Ren S, Richardson P, Rohner A, Sach N, Shao L, Smith G, Su R, Sun B, Timofeevski S, Tran P, Wang S, Wang W, Zhou R, Zhu J, Nair SK J Med Chem. 2023 | + | Design and Synthesis of Functionally Active 5-Amino-6-Aryl Pyrrolopyrimidine Inhibitors of Hematopoietic Progenitor Kinase 1.,Gallego RA, Bernier L, Chen H, Cho-Schultz S, Chung L, Collins M, Del Bel M, Elleraas J, Costa Jones C, Cronin CN, Edwards M, Fang X, Fisher T, He M, Hoffman J, Huo R, Jalaie M, Johnson E, Johnson TW, Kania RS, Kraus M, Lafontaine J, Le P, Liu T, Maestre M, Matthews J, McTigue M, Miller N, Mu Q, Qin X, Ren S, Richardson P, Rohner A, Sach N, Shao L, Smith G, Su R, Sun B, Timofeevski S, Tran P, Wang S, Wang W, Zhou R, Zhu J, Nair SK J Med Chem. 2023 Apr 13;66(7):4888-4909. doi: 10.1021/acs.jmedchem.2c02038. Epub , 2023 Mar 20. PMID:36940470<ref>PMID:36940470</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> | ||
</div> | </div> | ||
<div class="pdbe-citations 8fp1" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 8fp1" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Protein kinase C 3D structures|Protein kinase C 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
PKCeta kinase domain in complex with compound 2
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