Structure-based discovery of C-2 substituted imidazo-pyrrolopyridine JAK1 inhibitors with improved selectivity over JAK2
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Pharmacophore modeling of JAK1: A target infested with activity-cliffs
2020, Journal of Molecular Graphics and ModellingCitation Excerpt :However, only compounds of known stereochemistries, bioassayed using the same technique with inhibitory bioactivities reported as Ki values and were included in this study. Hence, 151 JAK1 inhibitors (1–151, Table S1 under Supporting Material) from published literature [19–25] were included in the present modelling. In cases where bioactivity values (Ki) were expressed as being higher than 3.5 μM (i.e., compounds 2, 3, 4, 5, 8, 10, 11, 12, 13, 16, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 32, 33, 35, 43, 44, 45, 48, 49, 50, 51, and 52 in Supplementary Table S1) we assumed the value to be 3.5 μM.
Putative dual inhibitors of Janus kinase 1 and 3 (JAK1/3): Pharmacophore based hierarchical virtual screening
2018, Computational Biology and ChemistryCitation Excerpt :For the docking analysis, appropriate crystal structures of JAK1 and JAK3 were selected among available structures of corresponding proteins. In the protein databank six crystal structures of JAK1 (PDB ID: 4EHZ, 4E4N, 4E5W, 4EI4, 4FK6, and 4E4L), and eight of JAK3 (PDB ID: 1YVJ, 4HVD, 3PJC, 4HVI, 4HVH, 4 HV G, 3LXK, and 3LXL) are reported (Zak et al., 2012; Kulagowski et al., 2012; Labadie et al., 2012; Boggon et al., 2005; Soth et al., 2012; Chrencik et al., 2010; Burns et al., 2009). All of these crystal structures were downloaded and prepared for docking analysis and were optimized in 'protein preparation' program of Schrödinger software.
Reactions of 3-Acylchromones with Heterocyclic Ketene Aminals: One-Pot Synthesis and Phosphatase Inhibitory Activity of Fused Pyridine Derivatives
2017, European Journal of Organic ChemistryEnsemble docking-based virtual screening yields novel spirocyclic JAK1 inhibitors
2016, Journal of Molecular Graphics and ModellingCitation Excerpt :Showing preference for JAK1 over JAK2, they are worth following up in future optimization studies aiming for selective JAK1 inhibitors. We have utilized three sources to collect ligand structures and activity data for retrospective purposes: the ChEMBL Kinase SARfari [19], the Thomson Reuters Integrity database [20] and primary literature [21–31]. From the collected compounds, we have assembled two ligand sets: a training and a test set, containing 62 and 59 known JAK1 inhibitors, respectively.
Anilino-monoindolylmaleimides as potent and selective JAK3 inhibitors
2014, Bioorganic and Medicinal Chemistry Letters