"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", stated H. Joseph Reiser, Ph.D., Chairman and Chief Executive Officer of Locus. "We have already demonstrated the power of our computational approaches and proprietary algorithms in our internal kinase programmes and in other kinase-related collaborations, so we expect to bring significant value to Ono's efforts against this target."
Protein kinases function as control switches for many biochemical pathways inside cells. Kinase activities can become disregulated by numerous molecular and signaling 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.
"We have dedicated ourselves to creating innovative medicines that will be truly beneficial to patients", stated Daikichi Fukushima, Ph.D., 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 one of the world's largest privately-owned Linux-based supercomputer clusters, Locus identifies optimum 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 synthesize only hundreds of compounds to generate highly potent lead molecules.
Locus Pharmaceuticals Inc. is a world expert in computational drug design. Locus has effectively integrated its proprietary computational approaches with in-house expertise in chemistry, biology and crystallography to create a competitive preclinical drug development platform. Locus is using its capabilities to develop its own compounds and has also entered into various drug design/development collaborations with pharmaceutical partners, including Ono. All of the company's internal development programmes emanate from its computational technology and are focused on oral drug therapies, principally in cancer and inflammation.
Locus has recently filed its first IND for LP-261, the company's lead oral oncology compound. In its inflammation programme, Locus created uniquely selective, first in class p38 inhibitors that bind to an allosteric binding site rather than the ATP site, which may offer an improved safety profile. Earlier stage projects include a programme to develop multi-kinase inhibitors, a Heat Shock Protein 90 programme which is being conducted in collaboration with the National Cancer Institute (NCI) and a gp41 programme for AIDS/HIV. Locus is a privately-held company.