Scientists discovered the compound eCF506, which effectively inhibits the growth of breast cancer cells in cell culture, zebrafish, and mouse xenograft models of the disease. This compound was more effective than existing medicines at targeting breast cancer cells because it more selectively inhibited SRC tyrosine kinase, a protein targeted by other medications that promotes growth of cancerous cells.1
“eCF506 is the first drug candidate of a second generation of SRC inhibitors that will not only help to understand the complexity of some cancers but also the development of safer combination therapies,” explained Asier Unciti-Broceta, PhD, Cancer Research Center, University of Edinburgh, Edinburgh, United Kingdom, and study leader.
Not only is eCF506 more selective for SRC tyrosine kinases, but also it does not affect other molecules in the cells. This compound, therefore, could be more effective and have fewer side effects than other drugs that are in development.
This study, published in the Journal of Medicinal Chemistry, identified eCG506 via imaging techniques that directly visualize the effects of candidate drugs on cells. eCG506 displayed excellent water solubility and oral bioavailability.
The compounded stopped SRC tyrosine kinase-associated tumor migration in a zebrafish model without causing life-threatening heart defects. eCF506 also decreased SRC tyrosine kinase activity in breast cancer xenografts in mice. Although these results are promising, further research is needed.
“This candidate drug will need to undergo further preclinical testing before it can be taken forward into clinical trials but these early findings are very promising,” said Neil Carragher, head of the Edinburgh Cancer Discovery Unit at the University of Edinburgh, and co-leader of the study.
“The result provides further support for our new drug discovery approach, which aims to deliver more effective medicines at reduced costs for patients and health care providers.”
The Medical Research Council, Wellcome Trust, and the commercialization catalyst Sunergos Innovations funded this research.
1. Fraser C, Dawson JC, Dowling R, et al. Rapid discovery and structure-activity relationships of pyrazolopyrimidines that potently suppress breast cancer cell growth via SRC kinase inhibition with exceptional selectivity over ABL kinase [published May 4, 2016]. J Med Chem. doi:10.1021/acs.jmedchem.6b00065.