Features of selective kinase inhibitors.

By Zachary A. Knight, Kevan M. Shokat. Chemistry and Biology, 2005

647 citations recorded by the source corpus.

Subfields: Hematology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c8a377ec6c9f85f94a57c326dd95dfbd8303700e

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Citations in the corpus

Rational Approaches to Improving Selectivity in Drug Design (2012, background): “10 In practice, absolute selectivity for a single kinase may be unattainable, but modulating the selectivity profile can lead to improved drug properties and in many cases hitting multiple kinases can be beneficial.”
Targeting the cancer kinome through polypharmacology (2010, neutral): “Although there are exceptions, the activity of most kinase inhibitors in cells correlates with biochemical parameters that can be measured in vitro , such as the dissociation constant (K D ) of the drug and the Michaelis–Menten constant for ATP binding (K M,ATP ) of the kinase 88 .”
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity (2011, background): “Potency of ATP-competitive kinase inhibitors in the cellular context is dictated not only by the intrinsic affinity of the inhibitor for the kinase, but also by the Michaelis-Menten constant for ATP binding and the cellular concentration of AT”
A Homogeneous, High-Throughput Assay for Phosphatidylinositol 5-Phosphate 4-Kinase with a Novel, Rapid Substrate Preparation (2013, background): “The Km of ATP (5–6 mM) had been determined previously [17,30], and the ATP concentration was set at the Km to ensure that the assay would be sensitive to ATP-competitive inhibitors.”
A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma. (2006, neutral): “Unfortunately, it remains challenging to predict which target combinations will be most effective in a speciﬁc cancer, and ge-netic inactivation of these targets rarely predicts the efﬁcacy of the corresponding small molecule drugs (Knight and Shokat, 2005).”
A quantitative analysis of kinase inhibitor selectivity (2008, background): “(S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene1,3(2H)-d ione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase C beta.”
A Pharmacological Map of the PI3-K Family Defines a Role for p110α in Insulin Signaling (2006, neutral): “In addition to these compensatory mechanisms, PI3-Ks possess kinase-independent signaling activities that can cause inhibitors and knock-outs to induce different phenotypes (Knight and Shokat, 2005; Vanhaesebroeck et al., 2005).”
Potential therapeutic applications of autophagy (2007, background): “This cautious optimism is partly based on a recent surge in reports of selective and potent kinase inhibitor”
Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors (2007, methodology): “Therefore, the validation of inhibitor selectivity mostly relies on data from large assay panels using recombinant enzymes and enzyme fragments, which are then correlated with results from cell-based assay”