More fantastic work from Iain Wallace of ChEMBL, below. These are maps of active antimalarials and predicted targets, expressed as similarity maps, i.e. with an extra level of analysis added on top. This provides a very intuitive way of walking through related compounds to compare structures. How best do we use this kind of analysis - as a target guide, or as a "prediction of what to make next" guide?
Jim Cronshaw here. Research on my side of the Todd Lab into the synthesis of two new anti-malarial drug candidates is progressing well. As a new honours student in the Todd group, unfamiliar with the ways of a research lab, I found myself inundated with the volume of new information coming my way, though I’ve settled in nicely now. This post is intended to summarise the work I’ve completed so far.
It's exciting as usual on the project. We've submitted the three compounds for in-vivo oral evaluation in a mouse model. The original hits TCMDC-123812 and -123794 were submitted along with one of Zoe's near neighbours, ZYH 3-1. It's not the most active of our compounds with an IC50 of 26 nM, but its logP comes in at just under 5 or there abouts (see: http://www.thesynapticleap.org/node/384#comment-798). It's still pretty high so we'll see how it goes.
Part of the first session at the Open Source Drug Discovery for Malaria meeting at The University of Sydney, February 24th 2012. Speaker is Dr Luigi Palombi, ANU.
Part of the first session at the Open Source Drug Discovery for Malaria meeting at The University of Sydney, February 24th 2012. Speaker is Dr Mary Moran, Policy Cures.
Welcome address at the Open Source Drug Discovery for Malaria meeting at The University of Sydney, February 24th 2012. Speaker is Professor Mary O'Kane, Chief Scientist and Engineer, New South Wales, Australia.
Opening remarks at the Open Source Drug Discovery for Malaria meeting at The University of Sydney, February 24th 2012. Speaker is Dr Mat Todd, The University of Sydney.
In August 2011 my lab started an open source drug discovery for malaria project. We’ve been a) very excited about this idea, and b) very busy getting things started. It’s an unusual project, exciting not only because we might be able to change the world, but because it’s not clear how we might do it. To me, that’s the definition of good research – you not only don’t know whether it’s going to work, but you don’t even know how to go about doing it.
One of the interesting features of the GSK set of antimalarial compounds that are acting as the starting point for this project is that they are whole-cell actives, meaning that though they are extremely promising hits, we don't know how they work - i.e. what the targets are. To some extent this doesn't matter - praziquantel has been used for over 30 years and nobody knows how it works.
In January the first biological data for compounds from the open source drug discovery for malaria project came through. The compounds were based on two hits identified in the GSK Tres Cantos set (TCMDC-123812 and TCMDC-123794). The two originals performed well, and we also identified two other compounds that looked promising (PMY 14-1 and PMY 14-3-A).
