Discovery Capabilities
Vernalis has a number of core competencies including chemistry, structural sciences, molecular modelling and assay development to ensure ongoing capability to evaluate new targets rapidly and identify innovative drug candidates. The Vernalis discovery capability bas been endorsed recently by a major oncology collaboration with French pharmaceutical company, Servier. Research has also been reorganised, with an increased focus on Vernalis’ three late-stage lead optimisation programmes addressing novel targets in cancer, neuropathic pain and diabetes. Two of these discovery programmes utilise Vernalis’ suite of competitive structure-based drug discovery technologies. This uses a fragment-based approach to identify novel chemical starting points for the drug discovery process, from which hit compounds are identified using NMR and other biophysical techniques. The evolution of these hits into lead compounds is guided by the way in which they bind to the target, determined by using X-ray crystallography. This approach delivered highly active clinical candidate molecules for the Hsp90 programme partnered with Novartis. The initial goal is to generate attractive development candidates from one to two ofthese programmes within the next 12 months.
Key late-stage discovery programmes:
Checkpoint Kinase 1(Chkl) inhibitors – Cancer
In cancer cells with a defective Gl checkpoint, the Chkl pathway is required to correct DNA damage, induced by clinically used cytotoxic agents e.g. gemcitabine and irinotecan. Some cancer cells use this checkpoint response to increase cell survival by pausing DNA replication and allowing repair of the damaged DNA before completing cell division. Inhibition of the Chkl kinase prevents this checkpoint response, forcing cells to undergo cell division (mitosis) with substantial DNA damage that results in their death. The aim of this programme is to identify product candidates that increase the anti-tumour efficacy of current cytotoxic agents without increasing their toxicity to non-cancerous tissues.
