Abstract
Cancer continues to present as an increasing and serious global unmet medical need in today's aging population.1 Macrocyclic kinase inhibitors have reached advanced clinical testing and are making an impact in oncologic conditions including myelofibrosis, lymphomas and leukemias. Rheumatoid arthritis (RA) is also beginning to be impacted with the first macrocycle having entered Phase I clinical evaluation in healthy volunteers. Increasing reports of innovative macrocycles in preclinical research are appearing in the literature. Desirable, selective, multi-kinase inhibitory profiles against specific kinases known to be abrogated in cancer, RA, and other diseases have been achieved in a first generation series of clinical stage compact small molecule macrocyclic kinase inhibitors. Herein we discuss their design, synthesis, structure activity relationships and assessment of the latest clinical data in a range of oncologic conditions. Macrocyclic kinase inhibitors have the potential to offer new hope to patients and their families.
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