It’s the assay...
How Genentech redesigned a discovery assay to find a specific Nav1.7 blocker
Genentech and Xenon have reported that the key to finding a selective Nav1.7 blocker is devising a better screen, not using a bigger compound library. By retooling a commonly used assay, the partners identified a new lead and established principals for tailoring screen construction to improve drug discovery for this and other ion channels.
Nav1.7 belongs to a family of voltage-gated sodium channels that show a high degree of sequence and structural conservation, making selective inhibition a challenge. Yet individual members play distinct roles in physiology and disease.
For example, Nav1.7 is expressed by neurons that transmit pain signals, and mutations in the channel cause pain disorders. Nav1.1, Nav1.2, Nav1.4 and Nav1.5 are expressed by different sets of neurons, and