The human caseinolytic Protease P (HsClpP) is a serine protease located in the mitochondria of human cells. Its role is to maintain a healthy mitochondrial proteome by removing damaged or badly folded proteins. As cancer cells are continually generating new proteins, they rely heavily on these types of proteases to avoid an accumulation of non-functional proteins. Activation of HsClpP by small molecules is therefore being investigated as a potential new mechanism of action to target certain cancers. Similarly, the selective activation of bacteria ClpP, such as SaClpP, could lead to new antibacterial agents with a new mechanism of action. In this presentation we will highlight the discovery and development of new selective HsClpP and SaClpP agonists.

Dr Grant McNaughton-Smith obtained his bachelor’s degree in chemistry from the University of Durham in England. His PhD (University of East Anglia, UK) focused on the synthesis of a family of macrolide natural products.
Following a postdoctoral research position with Prof. Stephen Hanessian at the Université de Montréal, which focused on the preparation of β-turn peptidomimetic scaffolds and hydroxyethylene bioisoteres, he joined a start-up biotech company called Ionpharma (Montréal) as a medicinal chemist targeting ion channel inhibitors for Raynaud’s disease.
Dr McNaughton-Smith was then recruited by ICAGEN, a bio-technology company focused on ion channel modulators based in Research Triangle Park, USA. There he led several drug discovery projects targeting a diverse range of diseases including, sickle cell disease, neuropathic pain, epilepsy and glaucoma.
His work in ICAGEN resulted in 4 IND submissions (human clinical studies) and more than 15 granted US patents.
Currently Dr McNaughton-Smith is the Director of R&D at CEAMED, SA and guides the research for the Fundación Canaria del Instituto Canario de Investigación del Cancer (FICIC) in La Laguna, Tenerife. Both entities are focused on generating potential new drugs for treatment resistant cancers.