View source for 4i5c


==The Jak1 kinase domain in complex with inhibitor==
<StructureSection load='4i5c' size='340' side='right'caption='[[4i5c]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4i5c]] 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=4I5C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I5C 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C5I:3-OXO-3-[(3R)-3-(PYRROLO[2,3-B][1,2,3]TRIAZOLO[4,5-D]PYRIDIN-1(6H)-YL)PIPERIDIN-1-YL]PROPANENITRILE'>C5I</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=4i5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i5c OCA], [https://pdbe.org/4i5c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i5c RCSB], [https://www.ebi.ac.uk/pdbsum/4i5c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i5c 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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The identification of a novel fused triazolo-pyrrolopyridine scaffold, optimized derivatives of which display nanomolar inhibition of Janus kinase 1, is described. Prototypical example 3 demonstrated lower cell potency shift, better permeability in cells and higher oral exposure in rat than the corresponding, previously reported, imidazo-pyrrolopyridine analogue 2. Examples 6, 7 and 18 were subsequently identified from an optimization campaign and demonstrated modest selectivity over JAK2, moderate to good oral bioavailability in rat with overall pharmacokinetic profiles comparable to that reported for an approved pan-JAK inhibitor (tofacitinib).

Novel triazolo-pyrrolopyridines as inhibitors of Janus kinase 1.,Hurley CA, Blair WS, Bull RJ, Chang C, Crackett PH, Deshmukh G, Dyke HJ, Fong R, Ghilardi N, Gibbons P, Hewitt PR, Johnson A, Johnson T, Kenny JR, Kohli PB, Kulagowski JJ, Liimatta M, Lupardus PJ, Maxey RJ, Mendonca R, Narukulla R, Pulk R, Ubhayakar S, van Abbema A, Ward SI, Waszkowycz B, Zak M Bioorg Med Chem Lett. 2013 Jun 15;23(12):3592-8. doi: 10.1016/j.bmcl.2013.04.018., Epub 2013 Apr 17. PMID:23642482<ref>PMID:23642482</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4i5c" 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: Fong R]]
[[Category: Lupardus PJ]]