A hERG assay was run on two compounds:
which were both positive (numbers were pIC50 = 5.6 and 5.2 while ideally we'd want compounds to be at about 4.5). This represents a warning flag, rather than a show-stopper - hERG is typically more of a problem with bases. Reducing this activity should be an aim of future analog design in OSM's Series 4 (http://openwetware.org/wiki/OpenSourceMalaria:Triazolopyrazine_%28TP%29_Series).
Future use of this assay: The assay employed in this case was a low-throughput patch-clamp assay. It would be useful to run a higher-throughput competitive binding assay for future analogs in OSM Series 4.
Appeal - Is there a lab willing to run a high throughput hERG competitive binding assay on future Series 4 compounds? Comments can be below, or via email to email@example.com, or via any other means of contacting members of the consortium listed on the landing page: http://opensourcemalaria.org/
More data should be coming #211
But still need collaborator lab long-term here.
AstraZeneca ran the latest hERG assay
The data obtained point to an ongoing need for screening of future compounds in this assay, as well as the need for a predictive model.