19th RSC/ SCI MEDICINAL CHEMISTRY SYMPOSIUM
MedChemNet and Infectious Diseases Hub were absolutely delighted to attend the first two days of the recent 19th RSC / SCI Medicinal Chemistry Symposium – Europe’s premier biennial Medicinal Chemistry event – focusing on first disclosures of significant new therapeutic agents across all disease areas and new strategies in medicinal chemistry.
The event assembled a variety of academic and industrial scientists engaged in all aspects of the drug discovery and development process and provided a forum for discussion of current topics and thinking at the forefront of medicinal chemistry. In this article, we give an over view of the session on neglected tropical diseases (NTDs), but you can find the reports for the full two days here and here.
New for the conference this year was a live webcast of the afternoon session on NTDs, an interesting and often overlooked area. This began with Kelly Chibale, from the University of Cape Town (South Africa), introducing the subject. Chibale emphasized the burden of these diseases on populations in the developing world and commented that, despite their significant burden and the progress that has been made, there is still a great deal of imbalance in the funding and research efforts given to these diseases. For, example only 1.4% of clinical trials and 1% of global health investment between 2000 and 2011 were in the NTD field.
The conference hall before the session on NTDs began.
Chibale then went on to describe his work on PI4K inhibitors as novel antimalarials, work that is part of H3D, the drug discovery and development center at Cape Town. He discussed the necessity of a novel antimalarial to fulfil criteria such as blocking transmission, oral administration and impact on all stages of the parasitic lifecycle then went on to report his findings on clinical and preclinical candidates MMV048 and UCT943.
In an alternative take on developing antimalarial drugs, Christoph Boss (Actelion Pharmaceuticals, Allschwil, Switzerland) then discussed the discovery and characterization of their phenylalanine-based compound, ACT-451840. He described the efforts from screening hit to the drug candidate, highlighting the positive preclinical trial results in mice and the completed Phase I study demonstrating safety and tolerability. However, Boss highlighted potential issues regarding the variability in Cmax between fed and fasted populations – something that could present an issue for this disease of poverty – and research will be ongoing.
The marquee, complete with posters and refreshments.
Looking at another major disease of poverty, tuberculosis, Rob Young from GlaxoSmithKline (UK), spoke on their efforts with open source collaboration to identify and progress non-covalent inhibitors of the mycobacterial enzyme DprE1. Young described the early stages of development, the molecular changes the compound underwent as the journey progressed (including truncation and a scaffold hop) and the mode of action studies undertaken to better understand the drug.
Moving back to focus on malaria, Jonathan Large from LifeArc (Stevenage, UK) followed, describing their class of imidazopyridines as inhibitors of the malarial signalling protein PfPKG. Their inhibitor has demonstrated good in vivo efficacy in rodents and appears to be selective when tested against a panel of human kinases. Large not only shared this data but also described some of the structure-activity relationship studies they have undertaken.
In the final presentation, we heard from Charles Mowbray from the Drugs for Neglected Diseases initiative (DNDi; Geneva, Switzerland). Mowbray discussed the DNDi’s candidates for the treatment of visceral and cutaneous leishmaniasis, including the optimization of a single hit discovered from a pool of ~100,000 compounds. The second generation compound, DNDi-3105581, has demonstrated promising preclinical data, and the DNDi hope this will now move into further development.
To conclude Mowbray again highlighted the challenges that are faced when tackling NTDs, such as the climate, lack of infrastructure, political instabilities and the nature of the population, who are often undernourished and may also be infected with multiple pathogens. He also took the opportunity to draw attention to the DNDi’s portfolio of drugs being developed for these diseases, including some exciting work towards a single dose cure in sleeping sickness.
The day concluded with flash poster sessions, including more research efforts into malaria and other topics not yet highlighted in the day such as treatments for Alzheimer’s.
AUTHORS: MARTHA POWELL, FUTURE SCIENCE GROUP
Watch Prof. Chibale's presentation here