Discovery Follows Successful Collaboration between Selcia, Cypralis and Gilead Sciences

17 September 2018

Cambridge and Ongar, UK, 17th September 2018 / Sciad Newswire / A paper entitled ‘Discovery of a Potent and Orally Bioavailable Cyclophilin Inhibitor Derived from the Sanglifehrin Macrocycle’ by authors from Selcia, Cypralis and Gilead has been selected as a featured article by the editors of The Journal of Medicinal Chemistry. 

The authors describe the identification of synthetic, macrocyclic, orally bioavailable cyclophilin inhibitors with potent HCV activity. These compounds also provide starting points for drug discovery programmes in several other major diseases where there is a high level of existing unmet need. This new class of macrocyclic cyclophilin inhibitors, designated as the “cyprolide” family, are highly potent, non-immunosuppressive, have low molecular weight and favourable drug properties. Currently, the only marketed cyclophilin inhibitor is cyclosporin A which causes immune-suppression via its interaction with calcineurin.  

Cypralis span out from Selcia in 2013 and wholly owns or has exclusive rights to over 2,000 cyclophilin inhibitors, representing one of the largest libraries of rationally designed cyclophilin inhibitors in the world. In January 2018, Gilead exclusively licensed to Cypralis the development and commercialization rights to certain cyclophilin inhibitors arising from the Gilead/Selcia collaboration, in all fields except for oncology and virology.  

Mike Peel Ph.D, Chief Scientific Officer at Cypralis, said: “Natural products often deliver attractive phenotypical responses that are difficult to reproduce with conventional ‘small molecules’, but their development can be challenging due to poor drug-like properties or raw material availability. The publication outlines the successful simplification of a very complex natural product lead, using structure-based design, to deliver compounds that retain the phenotypical responses of the natural product but are completely synthetic and have dramatically improved drug-like features including oral bio-availability, absence of drug interaction potential, and the ability to synthesize on a multi-kilogram scale. Cypralis is developing its first-in-class, non-immunosuppressive cyclophilin inhibitors as new therapies for degenerative diseases including Parkinson’s disease and fibrosis.”

Vicky Steadman Ph.D, Director of Discovery at Selcia, said: “Selcia, now part of the Eurofins Group, has a strong track record in Integrated Drug Discovery. The expertise of our predominantly ex-Big Pharma team had a significant impact from the outset on the successful completion of this project, in partnership with Gilead’s anti-viral research group. Following the completion of the HCV project with Gilead, Selcia is pleased to be continuing its collaboration with Cypralis to further explore the utility of cyprolides as potential clinical candidates in other disease areas.” 

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