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10th September 2013 @ 14:46

Very excited to introduce OSM Series 4 - a new chemical starting point for the project. This was announced today by MMV.

For a list of all the compounds inherited from MMV (structures and potencies) see: Updated Data on Amounts Remaining in MMV Stock of Series 4


Representative TP Compound

What makes this series unusual is the amount of specific investigatory work that has gone into it already. Series 1-3 started from compounds that had been discovered through a screen by Big Pharma, but no follow-up work was done, nor the development of an understanding of what the active compounds might be doing.

Series 4 comes to the project from MMV, who have decided to place all the data they have in the public domain - once again Paul Willis has been the OSM project champion here. The compound was also discovered by Big Pharma, and was investigated by them. The project was stopped (not because of any perceived shortcoming of the compounds) and was passed to MMV who have employed a CRO to investigate further. These two projects generated a lot of data, with much of it suggesting that the series looks very promising. Members of the series are potent antimalarials with good pharmacokinetic properties. These need improving, which is what OSM is now going to do in the public domain. Please join the consortium in exploring this new series.

Another interesting difference with Series 4 is that there is some suggestion of what the compounds are doing - they have come up positive in Kiaran Kirk's ion regulation assay, which implies that these compounds may be hitting PfATP4, a new an interesting target in antimalarial drug discovery. Kiaran's going to be carrying out this screen as a member of the consortium.

So there's lots to do. The series was announced today. All the data the OSM project has to date are now in the public domain. If you're a medicinal chemist you'll want to read through the briefing document from MMV for all the current details. If you know any chemists, ask them if they know of any molecules anywhere that look like these TPs. If they don't look busy, ask them if they'd like to make and share a molecule. If you know any biologists, ask them about what an ion regulation assay is and why these compounds can kill the malaria parasite and not the human host (how cool is that?). If you'd ilke to be involved in some other way, you can check out the non-science list - a project like this generates lots of non-lab-science tasks like writing and data curation and wiki maintenance.

You can comment below if you sign in through one of the ID providers (like Google) - you don't need to make an account - or you can get in touch in lots of other ways - look at the "Join the Team" tab on the Landing Page.

(Note to existing members of the consortium: In my lab in Sydney we're currently making some remaining compounds for Series 3, as is Patrick Thomson in Edinburgh, since there is great promise there, but it's likely we'll transfer attention to Series 4 fully once we have planned the first 10 Series 4 compounds to make and have established they are novel. Naturally this leaves Series 1-3 open to anyone to explore using the OSM infrastructure.)

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Attached Files
Representative TP Compound.cdx
Representative TP Compound.png