8fp3: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8fp3]] 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=8FP3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FP3 FirstGlance]. <br> | <table><tr><td colspan='2'>[[8fp3]] 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=8FP3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FP3 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=Y3I: | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</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=Y3I:3-[4-[(3~{R},5~{S})-3-azanyl-5-methyl-piperidin-1-yl]-6-chloranyl-7~{H}-pyrrolo[2,3-d]pyrimidin-5-yl]benzenecarbonitrile'>Y3I</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=8fp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fp3 OCA], [https://pdbe.org/8fp3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fp3 RCSB], [https://www.ebi.ac.uk/pdbsum/8fp3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fp3 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=8fp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fp3 OCA], [https://pdbe.org/8fp3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fp3 RCSB], [https://www.ebi.ac.uk/pdbsum/8fp3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fp3 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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 8fp3" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 8fp3" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Protein kinase C 3D structures|Protein kinase C 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Latest revision as of 12:51, 9 October 2024
PKCeta kinase domain in complex with compound 11PKCeta kinase domain in complex with compound 11
Structural highlights
Publication Abstract from PubMedImmune 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 Apr 13;66(7):4888-4909. doi: 10.1021/acs.jmedchem.2c02038. Epub , 2023 Mar 20. PMID:36940470[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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