5-(4-Phenoxybutoxy)psoralen (CAS 870653-45-5)

5-(4-Phenoxybutoxy)psoralen also referred to as AS-77 and PAP-1, is a blocker of the KCNA3 channel, specifically targeting the Kv1.3 channels. This compound shows potential for treating plaque psoriasis by interfering with the activation and proliferation of effector memory T cells, which are in the development of autoimmune diseases. Notably, PAP-1 reduces the secretion of TNFα by adipose tissue but does not affect the secretion of IL-6. Additionally, PAP-1 demonstrates the ability to inhibit the exocytosis of cytoplasmic granules from CD4(+)CD28(null) T cells. Its inhibitory effects are specific to Kv1.3 voltage-gated potassium channels, with an EC50 value of 2 nM at -80 mV in cells expressing the human channel. PAP-1 exhibits selectivity for Kv1.3 over a range of 22 ion channels, including potassium, sodium, calcium, and chloride channels, with EC50 values ranging from 45 to 15,000 nM. In experiments, PAP-1 inhibits the proliferation of isolated human CCR7- effector memory T cells induced by anti-CD3 antibodies. In vivo studies using rats have shown that PAP-1, at a dose of 3 mg/kg, can inhibit ovalbumin-induced delayed-type hypersensitivity.