Design for Selectivity – No Easy Task

golden key and puzzle

Neuropathic pain is a common and debilitating condition that affects over 7 million people. Current therapies are inadequate, and ion channels represent a promising, if challenging, therapeutic target. It is widely recognized that inadequate selectivity for ion channel targets can lead to unintended and profound effects. In this case study, the project team was challenged to design compounds with two layers of selectivity. First, the target in this case is a member of the HCN family, which includes four highly-related isoforms and there are known cardiac effects in drugs with no selectivity among these isoforms. Further, it was important to ensure the compound would be peripherally restricted (CNS impermeable), and demonstrated high selectivity against other cardiac ion channels, including hERG and Nav1.5. In this webinar, you can learn how the project team collaborated to design a screening strategy with these complex parameters in mind.

HOW THEY DID IT