Imatinib, a selective, small-molecule tyrosine kinase inhibitor, has life-saving clinical activity in certain cancers, but questions have been raised about the potential for cardiac toxicity through inhibition of its target, ABL kinase. In this issue of the JCI, Fernández et al. describe a novel method by which the ABL-inhibitory activity of imatinib was deleted by modifying its chemical structure (see the related article beginning on page 4044). The anticancer activity of the reengineered agent, called WBZ_4, was instead preserved against gastrointestinal stromal tumors in both in vitro and in vivo models via inhibition of KIT tyrosine kinase, and the desired safety was demonstrated with less cardiotoxicity of WBZ_4 compared with imatinib via the inhibition of JNK. The study shows that structural reengineering of a kinase-inhibitory drug to improve tolerability while preserving efficacy is feasible.
George D. Demetri
Usage data is cumulative from May 2020 through May 2021.
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.