On the Use of 2,5-Dimethyl-Pyrrol-1-yl-Benzoic Acid Derivatives as EPH-Ephrin Antagonists

Since their discovery as EPH receptor inhibitors in 2008 (1),2,5-dimethyl pyrrol-1-yl-benzoic acid derivatives 1 and 2 (Fig. 1) have been used as pharmacological tools aimed at elucidating the role of EPH kinases in pathological conditions (2, 3). Com-pounds 1 and 2 were originally found to block the binding of ephrin A5 to EPHA2 receptor with inhibitory potency in the low micromolar range, i.e.,with50%inhibitory concentrations (IC50s)of 65 and 33M, respectively (1). In a recent issue of Journal of Virology, Hahn andDesrosiers (4) observed that 2,5-dimethylpyrrol-1-yl-benzoic acid derivatives were significantly less potent at preventing EPH-ephrin interac-tions than what was originally reported by Noberini et al (1). The IC50 for inhibition of the ephrin A5 interaction with EPHA2 was estimated to be 1,683 M for compound 1 and 2,000 M for compound 2. To explain this considerable discrepancy, Hahn and Desrosiers (4) suggested that different assay conditions and re