Identification of synthetic, macrocyclic, orally bioavailable cyclophilin inhibitors with potent HCV activity, published in The Journal of Medicinal Chemistry
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.”
For further information, contact:
Simon Kerr, CEO
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Vicky Steadman, Director of Discovery
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Sciad Communications, Media Relations
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Notes for Editors
Cypralis is a company focusing on discovering and developing novel medicines for acute and chronic degenerative diseases. It was spun out from Selcia Ltd (Ongar, Essex) in 2013 to exploit its extensive expertise and know-how in targeting peptidyl-prolyl isomerases (known as PPIases), a large family of druggable protein targets.
The compounds described in the The Journal of Medicinal Chemistry paper are examples of a new class of fully synthetic cyclophilin inhibitors that Cypralis has designated as ‘cyprolides’. They are highly potent, non-immunosuppressive, low molecular weight cyclophilin inhibitors with excellent drug properties. These compounds are potent inhibitors of cyclophilin D and protect against opening of the mitochondrial permeability transition pore. This property leads to protection of cells and tissues associated with several diseases such as neurodegeneration, fibrosis and other mitochondrially-mediated diseases.
Cypralis is dedicated to the development of innovative cyclophilin inhibitors and expects to build upon its existing intellectual property estate through its own R&D activities and also through risk-sharing collaborations with pharmaceutical companies.
For further information visit http://www.cypralis.com
Selcia Ltd is a UK-based provider of integrated drug discovery services with a worldwide client base. Founded in 2001, its workforce comprises industry experienced medicinal chemists, biologists and ADME scientists as well as 14C radiolabeling experts. Selcia announced its acquisition by Eurofins earlier this year.
For further information visit: http://selcia.com
Eurofins – a global leader in bio-analysis Eurofins Scientific through its subsidiaries (hereinafter sometimes “Eurofins” or “the Group”) believes it is a scientific leader in food, environment and pharmaceutical products testing and in agroscience CRO services. It is also one of the independent market leaders in certain testing and laboratory services for genomics, discovery pharmacology, forensics, CDMO, advanced material sciences and for supporting clinical studies. In addition, Eurofins is one of the emerging players in specialty clinical diagnostic testing in Europe and the USA. With over 38,000 staff in more than 400 laboratories across 44 countries, Eurofins offers a portfolio of over 150,000 analytical methods for evaluating the safety, identity, composition, authenticity, origin and purity of biological substances and products, as well as for innovative clinical diagnostic. The Group objective is to provide its customers with high-quality services, accurate results on time and expert advice by its highly qualified staff.
Eurofins is committed to pursuing its dynamic growth strategy by expanding both its technology portfolio and its geographic reach. Through R&D and acquisitions, the Group draws on the latest developments in the field of biotechnology and analytical chemistry to offer its clients unique analytical solutions and the most comprehensive range of testing methods.
As one of the most innovative and quality oriented international players in its industry, Eurofins is ideally positioned to support its clients’ increasingly stringent quality and safety standards and the expanding demands of regulatory authorities around the world.
The shares of Eurofins Scientific are listed on the Euronext Paris Stock Exchange (ISIN FR0000038259, Reuters EUFI.PA, Bloomberg ERF FP).
For further information visit: http://eurofins.com