Identification of novel scorpion venom peptide inhibitors of the Kv1.3 ion channel and their potential as drug discovery leads for human T-cell mediated disease

Activated effector memory T-cells (T_EM) have been implicated in the pathogenesis of autoimmune diseases.¹ Activated T_EM cells express high levels of the voltage-gated potassium channel K_v1.3, which functions to control cell excitability. Inhibition of K_v1.3 reduces the release of pro-inflammatory mediators, inhibits T-cell proliferation and migration to inflamed tissues, and has been shown to ameliorate autoimmune disease symptoms in preclinical animal models. However, small molecule K_v1.3 inhibitors have failed to deliver a successful drug into the clinic, in part due to lack of potency and selectivity.