4USD

Human STK10 (LOK) with SB-633825

Summary for 4USD

• Entry DOI: 10.2210/pdb4usd/pdb
• Related: 4USE 4USF
• Descriptor: SERINE/THREONINE-PROTEIN KINASE 10, 4-{5-(6-methoxynaphthalen-2-yl)-1-methyl-2-[2-methyl-4-(methylsulfonyl)phenyl]-1H-imidazol-4-yl}pyridine (2 entities in total)
• Functional Keywords: transferase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 69564.37

Authors

Elkins, J.M.,Salah, E.,Szklarz, M.,von Delft, F.,Canning, P.,Raynor, J.,Bountra, C.,Edwards, A.M.,Knapp, S. (deposition date: 2014-07-07, release date: 2015-07-22, Last modification date: 2024-05-08)

Primary citation

Elkins, J.M.,Fedele, V.,Szklarz, M.,Abdul Azeez, K.R.,Salah, E.,Mikolajczyk, J.,Romanov, S.,Sepetov, N.,Huang, X.P.,Roth, B.L.,Al Haj Zen, A.,Fourches, D.,Muratov, E.,Tropsha, A.,Morris, J.,Teicher, B.A.,Kunkel, M.,Polley, E.,Lackey, K.E.,Atkinson, F.L.,Overington, J.P.,Bamborough, P.,Moller, S.,Price, D.J.,Willson, T.M.,Drewry, D.H.,Knapp, S.,Zuercher, W.J.
Comprehensive Characterization of the Published Kinase Inhibitor Set.
Nat.Biotechnol., 34:95-, 2016

PubMed Abstract: Despite the success of protein kinase inhibitors as approved therapeutics, drug discovery has focused on a small subset of kinase targets. Here we provide a thorough characterization of the Published Kinase Inhibitor Set (PKIS), a set of 367 small-molecule ATP-competitive kinase inhibitors that was recently made freely available with the aim of expanding research in this field and as an experiment in open-source target validation. We screen the set in activity assays with 224 recombinant kinases and 24 G protein-coupled receptors and in cellular assays of cancer cell proliferation and angiogenesis. We identify chemical starting points for designing new chemical probes of orphan kinases and illustrate the utility of these leads by developing a selective inhibitor for the previously untargeted kinases LOK and SLK. Our cellular screens reveal compounds that modulate cancer cell growth and angiogenesis in vitro. These reagents and associated data illustrate an efficient way forward to increasing understanding of the historically untargeted kinome.

PubMed: 26501955
DOI: 10.1038/NBT.3374

Experimental method

X-RAY DIFFRACTION (3.05 Å)