Cypralis, Selcia and Gilead publish synthetic macrocyclic cyclophilin inhibitors inspired by natural product sanglifehrin A
Cambridge, UK, 10th February 2017 / Cypralis, with colleagues from Selcia and Gilead Sciences Inc., have published in the Journal of Medicinal Chemistry a novel strategy of structural simplification of a natural product to generate synthetically tractable cyclophilin inhibitors for the treatment of HCV.
Cyclophilin inhibitors on the market or in clinical trials are cyclosporin (a natural product) or cyclosporin derivatives; the generation of potent, drug-like molecules through chemical synthesis has been challenging. Cypralis’s collaboration with Selcia and Gilead delivered a set of synthetic macrocyclic cyclophilin inhibitors inspired by the core structure of the natural product sanglifehrin A.
The paper describes how novel macrocyclic non-immunosuppressive cyclophilin inhibitors, with high potency in both biochemical and antiviral assays were generated by employing structure based drug design, modern synthetic methods and deep understanding of the property profile required of a successful drug.
Mike Peel, CSO of Cypralis, said: ‘The discovery of completely synthetic and very potent cyclophilin inhibitors that fully reproduce the biology of a semi-synthetic natural product lead is a major breakthrough in this field. It opens up many new opportunities for Cypralis’ drug discovery programmes in conjunction with our colleagues at Selcia and Gilead.’
Vicky Steadman, Director of Discovery at Selcia, said: ‘This ambitious strategy was feasible due to the combination of expertise in peptidyl prolyl isomerase biology, medicinal and synthetic chemistry available at Selcia with the deep virology and structural biology knowledge and commitment to the project at Gilead.’
This approach of structural simplification of a natural product opens up multiple avenues for the generation of novel intellectual property, and has generated several patents that are jointly owned by Cypralis and Gilead.
For further information, contact:
Simon Kerr, CEO
T: +44 (0)1277 367 020
Sciad Communications, Media Relations
Deborah Cockerill, Managing Partner
T: +44 (0)20 7470 8801
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. Cypralis is dedicated to the development of highly innovative therapeutics through inhibition of PPIases 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 is a privately held contract research organisation providing integrated small molecule drug discovery with specialist expertise in the medicinal chemistry of macrocycles, including cyclic peptides, their simplification and optimisation for drug use together with a unique peptidyl prolyl isomerase (PPIase) inhibitor screening platform. Selcia is also a global leader in radiochemistry providing 14C GMP radiolabelled API for clinical trials and 14C custom radiolabelling for drug metabolism, dermal penetration and environmental fate studies. For further information visit http://www.selcia.com