Targeting the cancer kinome through polypharmacology

By Zachary A. Knight, Henry Lin, Kevan M. Shokat. Nature Reviews. Cancer, 2010

673 citations recorded by the source corpus.

Kinase inhibitors are the largest class of new cancer drugs. However, it is already apparent that most tumours can escape from the inhibition of any single kinase. If it is necessary to inhibit multiple kinases, how do we choose which ones? In this Opinion article, we discuss some of the strategies that are currently being used to identify new therapeutic combinations of kinase targets.

Subfields: Molecular Biology, Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/219d7cb762f26aa16a5745d97339ee9695b760af

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In Molecular Biology

In Oncology

Tudor I. Oprea

Citations in the corpus

Automated design of ligands to polypharmacological profiles (2012, neutral): “1 3 10(25)); (4) the 2,3-dihydro-indol-1-yl analogues (compounds 12 and 13); and (5) the morpholino analogues (compounds 14–29)—of the 540 ligand–target associations, 437 were correctly predicted (P , 2.”
Kinase-targeted cancer therapies: progress, challenges and future directions (2018, background): “Further, in some cases, the combinations of kinase targeting agents reduced patient survival compared with the treatment using single drug [281].”
ChemProt: a disease chemical biology database (2010, background): “These studies are often focused on specific protein families, such as G-protein coupled receptors (8), nuclear receptors (9) and kinases (10), but global pharmacology profiles of chemicals are considered as well (1,2).”
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity (2011, background): “Despite the promise of polypharmacology, it remains a difficult technical challenge to rationally develop single compounds with a desired target spectru”
Large‐scale image‐based screening and profiling of cellular phenotypes (2017, background): “There is also an increasing interest to screen or design polypharmacological compounds that can inhibit multiple intra-cellular targets, which may lead to more effective but less toxic therapeutic agents (57).”
Comprehensive analysis of kinase inhibitor selectivity (2011, background): “The assay panels further have enabled a novel approach to kinase inhibitor discovery, based on screening entire libraries of compounds against panels of kinases, which has resulted in the discovery of several promising new inhibitor”