Psora-4

The lymphocyte potassium channel Kv1.3 is regarded as a new target for immunosuppression. Psora-4 is the most potent small-molecule Kv1.3 blocker known. It blocked Kv1.3 in a use-dependent manner, with a Hill coefficient of 2 and an EC₅₀ value of 3 nM, by preferentially binding to the C-type inactivated state of the channel. It exhibited 17- to 70-fold selectivity for Kv1.3 over closely related Kv1-family channels (Kv1.1, Kv1.2, Kv1.4, and Kv1.7) with the exception of Kv1.5 (EC50, 7.7 nM) and showed no effect on human ether-a-go-go-related channel, Kv3.1, the calcium-activated K⁺ channels (IKCa1, SK1-SK3, and BKCa), or the neuronal NaV1.2 channel. In a test of in vivo toxicity in rats, Psora-4 did not display any signs of acute toxicity after five daily subcutaneous injections at 33 mg/kg body weight. Psora-4 selectively suppressed the proliferation of human and rat myelin-specific effector memory T cells with EC₅₀ values of 25 and 60 nM, respectively, without persistently suppressing peripheral blood naive and central memory T cells. Because autoantigen-specific effector memory T cells contribute to the pathogenesis of T cell-mediated autoimmune diseases such as multiple sclerosis, Psora-4 and other Kv1.3 blockers may be useful as immunomodulators for the therapy of autoimmune disord.

This compound is featured on the Potassium Channels page of the Handbook of Receptor Classification and Signal Transduction. To browse other handbook pages, click here.