Cancer Research UK Edinburgh Centre

ECRC scientists develop new Src inhibitor with unique properties

Congratulations to members of the Edinburgh Cancer Discovery Unit (ECDU) at the centre: 23 May 2016

ECRC scientists develop new Src inhibitor with unique properties

Congratulations to members of the Edinburgh Cancer Discovery Unit (ECDU) at the ECRC whose paper entitled “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” has been recently published in the “Journal of Medicinal Chemistry” - a leading journal in the field of medicinal chemistry published by the American Chemical Society. The paper describes the development of a highly potent and orally bioavailable inhibitor of the non-receptor tyrosine kinase Src called, eCF506 (UK Patent Application GB1508747.1 submitted). In contrast to other Src inhibitors, eCF506 displays high selectivity towards Src tyrosine kinase without inhibiting many other kinases present in the cells. This is an important discovery because Src involvement in tumour progression and metastasis is well documented (Src was the first oncogene ever discovered in the human genome and its mutant constitutively-active form is transmitted by some oncogenic viruses). All other currently available Src-inhibitors (many of which are in clinical trials) do also inhibit other kinases, in particular Abl, which might result in lower anti-cancer activity in some tumour types and undesired side effects.

According to Dr Asier Unciti-Broceta; “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”. Another key feature of the article is the novel strategy used to discover eCF506, which represents a more rapid and cost effective approach compared with traditional drug discovery methods."

Professor Neil Carragher from the CRUK Edinburgh Centre says; “The short time frame and reduced costs required to discover a potential drug candidate of the quality of eCF506 is unprecedented”. Implementation of new drug discovery approaches such as those being pioneered within the ECDU may contribute to increased efficiency of drug discovery, providing more effective medicines at reduced cost for patients and healthcare authorities such as the NHS”.

Obviously more investigations are required to further validate the inhibitor and to assess the potential clinical utility of eCF506, but the published research is a great testimony to quality and efficiency of work performed by the ECDU and represents the first drug discovery program developed in full (from initial idea and drug design to synthesis and biological evaluation) in the CRUK Edinburgh Centre. We are confident that the ECDU and its directors (Asier Unciti-Broceta, Neil Carragher, Val Brunton and Margaret Frame ) will make every possible effort to maximise the utility and future impact of the exciting discoveries described in the paper.

Paper: Fraser C, Dawson JC, Dowling R, Houston DR, Weiss JT, Munro AF, Muir M, Harrington L, Webster SP, Frame MC, Brunton VG, Patton EE, Carragher NO, Unciti-Broceta A. 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. J Med Chem. 2016 May 4. [Epub ahead of print]

Link: http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.6b00065

University of Edinburgh news: http://www.ed.ac.uk/news/2016/breast-cancer-drug-hope