EC50: 3 nM
Psora 4 is a Kv1.3 blocker.
The voltage-gated Kv1.3 channel and the Ca2+-activated IKCa1 channel has been reported to promote and sustain Ca2+ signaling in human T cells via providing the driving force for Ca2+ entry through voltage-independent Ca2+ channels. Selective blockade of Kv1.3 and/or IKCa1 leads to membrane depolarization, reduced Ca2+ entry, as well as diminished cytokine proliferation and production.
In vitro: Psora-4 could block Kv1.3 in a dose-dependent manner. Psora-4 was found to be the most potent small-molecule Kv1.3 blocker known. Psora-4 exhibited 17- to 70-fold selectivity for Kv1.3 over Kv1-family channels including Kv1.1, Kv1.2, Kv1.4, and Kv1.7 and also showed no effect on human ether-a-go-go-related channel, Kv3.1, or the neuronal NaV1.2 channel. In addition, Psora-4 could suppress the proliferation of rat and human myelin-specific effector memory T cells with EC50 values of 60 and 25 nM, respectively, without persistently suppressing the peripheral blood naive and central memory T cells [1].
In vivo: In a study of in vivo toxicity in rats, Psora-4 was found not to show any signs of acute toxicity following five daily subcutaneous injections at 33 mg/kg body weight [1].
Clinical trial: N/A
Reference:
[1] Vennekamp J,Wulff H,Beeton C,Calabresi PA,Grissmer S,Hnsel W,Chandy KG. Kv1.3-blocking 5-phenylalkoxypsoralens: a new class of immunomodulators. Mol Pharmacol.2004 Jun;65(6):1364-74.