View source for 5hx8


==Jak1 complex with 4-[(4-aminocyclohexyl)amino]-3-(1H-benzimidazol-2-yl)-1H-pyridin-2-one==
<StructureSection load='5hx8' size='340' side='right'caption='[[5hx8]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5hx8]] 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=5HX8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HX8 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=66P:4-[(4-AMINOCYCLOHEXYL)AMINO]-3-(1H-BENZIMIDAZOL-2-YL)-1H-PYRIDIN-2-ONE'>66P</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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=5hx8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hx8 OCA], [https://pdbe.org/5hx8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hx8 RCSB], [https://www.ebi.ac.uk/pdbsum/5hx8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hx8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/JAK1_HUMAN JAK1_HUMAN] Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.
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== Publication Abstract from PubMed ==
The mammalian Janus Kinases (JAK1, JAK2, JAK3 and TYK2) are intracellular, non-receptor tyrosine kinases whose activities have been associated in the literature and the clinic with a variety of hyperproliferative diseases and immunological disorders. At the onset of the program, it was hypothesized that a JAK1 selective compound over JAK2 could lead to an improved therapeutic index relative to marketed non-selective JAK inhibitors by avoiding the clinical AEs, such as anemia, presumably associated with JAK2 inhibition. During the course of the JAK1 program, a number of diverse chemical scaffolds were identified from both uHTS campaigns and de novo scaffold design. As part of this effort, a (benz)imidazole scaffold evolved via a scaffold-hopping exercise from a mature chemical series. Concurrent crystallography-driven exploration of the ribose pocket and the solvent front led to analogs with optimized kinome and JAK1 selectivities over the JAK2 isoform by targeting several residues unique to JAK1, such as Arg-879 and Glu-966.

Structure-based design and development of (benz)imidazole pyridones as JAK1-selective kinase inhibitors.,Simov V, Deshmukh SV, Dinsmore CJ, Elwood F, Fernandez RB, Garcia Y, Gibeau C, Gunaydin H, Jung J, Katz JD, Kraybill B, Lapointe B, Patel SB, Siu T, Su H, Young JR Bioorg Med Chem Lett. 2016 Apr 1;26(7):1803-8. doi: 10.1016/j.bmcl.2016.02.035., Epub 2016 Feb 19. PMID:26927423<ref>PMID:26927423</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5hx8" style="background-color:#fffaf0;"></div>

==See Also==
*[[Janus kinase 3D structures|Janus kinase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Su HP]]