ML277

Description: ML277 (formerly known as CID53347902) is a novel, potent and selective activator of the K(v)7.1 (KCNQ1) potassium channel with EC50 of 270 nM. It was identified from a high-throughput screen utilizing a depolarization-triggered thallium influx through KCNQ1 channels which was developed and used to screen the MLSMR collection of over 300, 000 compounds. An iterative medicinal chemistry approach was initiated and from this effort, ML277 was identified as a potent activator of KCNQ1 channels (EC(50)=260 nM). ML277 was shown to be highly selective against other KCNQ channels (> 100-fold selectivity versus KCNQ2 and KCNQ4) as well as against the distantly related hERG potassium channel.

References: Bioorg Med Chem Lett. 2012 Sep 15; 22(18):5936-41