Protein kinases function as control switches for many biochemical pathways inside cells. Kinase activities can become dysregulated by numerous molecular and signalling events, thus contributing to both the onset and progression of diseases.
These proteins are of particular interest as targets for the development of novel therapeutics, but because there are more than 500 structurally related kinases, a drug often requires high selectivity for the intended target, a design capability where Locus has demonstrated expertise.
Under the terms of the agreement, Locus will apply its proprietary computational technologies, and capabilities in chemistry, biology and crystallography to design and develop IND-directed preclinical drug candidates for Ono. Financial and other terms of the agreement were not disclosed.
"We have dedicated ourselves to creating innovative medicines that will be truly beneficial to patients," said Daikichi Fukushima, executive director of Research Headquarters, Ono.
"This collaboration with Locus, a world leader in computational drug discovery technologies, is a great chance for Ono to strengthen its drug discovery capabilities."
Starting with a protein crystal structure, an in silico collection of 40,000 molecular fragments and Linux-based supercomputer clusters, Locus identifies ligand binding sites on protein targets, computes the binding affinity of molecular fragments to those sites and then links fragments with desirable chemical properties to computationally assemble virtual drug candidates.
The result is a 'virtual library' of drug candidates that exceeds the size and diversity of any physical screening library by orders of magnitude.
In addition, Locus can simulate physically realistic protein motions on very long-range timescales which can be used to validate the biological relevance of novel binding sites that may be uncovered by fragment mapping studies.
Because of the speed and accuracy with which these virtual libraries are constructed and evaluated, Locus typically needs to synthesise only hundreds of compounds to generate highly potent lead molecules.
"We look forward to this multi-year collaboration with Ono, which allows us to apply and leverage all of our internal drug development capabilities as well as our kinase knowledge-base," said Joseph Reiser Chairman and Chief Executive Officer of Locus.
"We have already demonstrated the power of our computational approaches and proprietary algorithms in our internal kinase programs and in other kinase-related collaborations, so we expect to bring significant value to Ono's efforts against this target," he added.
Kinases are implicated in many diseases, such as cancer, diabetes, cardiovascular disease, and neurological disorders.
It is estimated that kinase malfunction contributes to more than 400 diseases and that greater than 20 per cent of the drug discovery efforts are focused on protein kinase inhibitors.
Researchers require technologies that will enable them to rapidly develop assays that provide data for these potentially important kinase inhibitors.