We identify and develop small molecules, as either chemical tools to explore basic biology or as drugs to treat disease. We pursue mechanisms controlling calcium signalling and treatments for psychological disorders such as bipolar.
We are interested in small molecules that are in cells to control function or that can be added to alter function. We focus on two areas: first, basic biology related to calcium signalling with emphasis on the messengers NAADP, cyclic ADP-ribose and inositol phosphates; second, applied research in which we exploit findings from basic biology to identify novel drug targets for which we discover and develop new drugs.
We delight in addressing basic biological questions with small molecules through techniques such as measurement, radioactive labelling, synthesis and computational chemistry. Chemical tools that we have developed include cell-permeant, caged and radioactive forms of cyclic ADP-ribose and NAADP as well as the NAADP inhibitor Ned-19. We are gratified that these chemical tools are widely adopted and several are commercially available.
We are exploiting our expertise in basic cellular signalling to identify niche areas of opportunity not being pursued by industry. For example, we identified ebselen through repurposing as a lithium mimetic, and have progressed it from drug target, through mouse into man. Ebselen is now being taken into a phase 2 clinical trails for efficacy in bipolar disorder through a licensing deal with the biotech Sound Pharmaceuticals. Additionally, to facilitate translation of our research into treatments, in collaboration with colleagues in Pharmacology, we now have formed a start-up company, IntraBio.
Current Research Projects
- Identification of endogenous synthetic and degradation pathways for NAADP and their regulation.
- Chemical structure-activity relationships for NAADP and Ned-19 in relation to calcium release and receptor desensitization.
- Development of agonists and antagonists for cyclic ADP-ribose.
- Physiological regulation of inositol monophosphatase and the mechanism of inhibition by ebselen.
- The effects of ebselen in man through both experimental medicine studies and clinical trials.
Article in Nature highlighting our repurposing success - Can you teach old drugs new tricks?
Ebselen patent licensed to a biotech - Sound Pharmaceuticals and Oxford collaborate on a new treatment for bipolar disorder
Article in Chemical and Engineering News highlighting our repurposing efforts
Article in the Economist highlighting our repurposing efforts - Teaching old pills new tricks
Ned-19 virtual screening paper ranked in top 20 ligand-based virtual screening publications - State-of-the-art in ligand-based virtual screening
Free database of all commercially available compounds and screening software - http://zinc15.docking.org and – http://pubs.acs.org/doi/abs/10.1021/acs.jcim.5b00559
Software potentially free to academics - http://www.eyesopen.com
Commercially available compounds