Background:The guanine exchange factor Epac is a cAMP sensor. Results: We have identified a tetrahydroquinoline analog named CE3F4 that blocks Epac activation in response to cAMP in vitro and in living cultured cells. Conclusion: CE3F4 behaves as an uncompetitive antagonist of Epac with respect to cAMP. Significance: CE3F4 may serve as a basis for the development of new therapeutic drugs.

Drug screening for antimalarials uses heme biocrystallization inhibition methods as an alternative to parasite cultures, but they involve complex processes and cannot detect artemisinin-like molecules. The described method detects heme-binding compounds by mass spectrometry, using dissociation of the drug-heme adducts to evaluate putative antiplasmodial activity. Applied to a chemical library, it showed a good hit-to-lead ratio and is an efficient early stage screening for complex mixtures like natural extracts.