mattodd
commented
8 years ago Hi @cdsouthan. Thanks for this suggestion. I discussed something like this a year or so ago with some people about the compounds that did make it into the MMV boxes: how about we do something to make sure that the malaria box or pathogen box compounds have readily available, open synthetic routes and/or are always physically available in some way? I had heard that people who had discovered interesting things with the MBox compounds wanted to follow up those findings, but then were stuck on how to get more. I don’t know to what extent that was a problem - perhaps a biology lab with no available chem collaborators who wanted compounds that had arisen from libraries and for which no bulk material was available? Perhaps CRO resynthesis was expensive if there was no published precedent. I’m sure ways were found in the cases of particularly promising compounds.
A paper is I think forthcoming ( @PaulWillisMMV ? ) on the experience on the MBox, but as I understand it people in the end took a variety of approaches to source more compounds, ranging from purchase through to local resynthesis. Obviously in OSM Series 1 we used resynthesis. These solutions are pretty generic and would work for good-looking compounds that didn’t make the cut for inclusion in the Pathogen Box.
For the Pathogen Box compounds themselves I’m not sure of the current/proposed approach. Perhaps the CROs involved will be willing to share lab notebooks, though that still leaves the pre-existing commercial compounds. My sense is that there should be a site somewhere (we could easily host, and have offered to do so) in which each compound has a chemical recipe, and people who attempt to reproduce that work can post their own suggestions/spectra/data. A community-driven compendium of resynthesis. Clearly this would work too for the compounds that did not make it, and is at the heart of what OSM does.
The other option is what you suggest - having some compounds of interest be commercially available. There is merit to this even if the data are open since in many cases people may want to buy for convenience/speed or because there is no local synthesis resource. If there’s a market, then why not? It is likely this is already being considered by suppliers to the Pathogen Box.
As far as OSM is concerned we can certainly nominate exemplar compounds from each series, plus ample synthetic precedence. SAR controls are easy if you want negatives :) Could be a nice way to promote continued interest in compounds we may have put on back burners, and yes to help promote their broader evaluation.
Is this what you mean? OSM compounds, and those that didn’t make it, being offered commercially even when there are open (source) routes to their synthesis available?
PaulWillisMMV
drc007
cdsouthan
madgpap
Consequent to a colloquial vendor contact at a recent meeting (who I need not identify just yet) we discussed the idea of (them) offering selected OSM leads for sale and/or other leads from that are likely to not have made it into the MMV Pathogen box (when we finaly get to see the structures that did make it)
http://cdsouthan.blogspot.se/2014/06/getting-into-box-with-some-recent.html
While a commercial exersise by definition, it would still be a way of expediting open data sharing. This would be particularly so since lead swapping for antimalarial teams to cross-test probaly does not happen as much as it could and open groups obviously sythesize at a relatively small scale that make this difficult anyway. This could also facilitate molecular target cross screening for mechanism of action deconvolution.
If this idea has any merit would anyone from OSM care to pick out maybe one lead from each series that could be canidates for this? (I could have a go but dont know the sets so well). NOBA, choosing chemotype-matched SAR controls could also be useful (i.e usual principal of chemistry as similar as possible but with activitues as far apart as possible - at least an order of magnitude)