UK-78282 (hydrochloride)

UK-78282 hydrochloride is a K_V1.3 channel inhibitor with an IC₅₀ value of 0.20 μM and a K_d of 0.39 μM. UK-78282 hydrochloride also inhibits the Kv1.4 Potassium Channel. UK-78282 hydrochloride blocks KV1.3 in a use-dependent manner and inhibits human T lymphocyte activation by regulating the cell cycle. UK-78282 hydrochloride can be used in research related to mental disorders, such as depression and schizophrenia^[1][2]. IC50 & Target:IC50: 200 nM (Kv1.3)^[1] In Vitro:UK‑78282 hydrochloride blocks Kv1.3 channel function in various cell models. Under acute administration conditions, this compound blocks native Kv1.3 channels in human peripheral blood T lymphoblasts (IC₅₀ = 202 nM), recombinant Kv1.3 channels in L929 cells (IC₅₀ = 280 nM), and Kv1.3 channels in RBL cells (IC₅₀ = 333 nM); it inhibits Kv1.3-mediated ⁸⁶Rb efflux in human T cells (IC₅₀ = 0.4 μM); and it inhibits the binding of ¹²⁵I‑ChTX to Kv1.3 expressed in HeLa cells (IC₅₀ = 0.7 μM)^[1].
UK‑78282 hydrochloride produces use-dependent block of Kv1.3 channels in human peripheral blood T lymphoblasts; the longer the duration of depolarizing pulses, the faster the establishment of steady-state block. Maintaining the holding potential at -50 mV to increase the proportion of C-type inactivated channels enhances the blocking efficacy of this compound^[1].

UK-78282 hydrochloride binds to an internal site of the Kv1.3 channel in human peripheral blood T lymphoblasts. This site overlaps with the binding site of verapamil, but does not overlap with the binding sites of extracellular ChTX or intracellular TEA^[1].
UK-78282 hydrochloride exhibits selectivity for Kv1.3 and Kv1.4 channels over other Kv family channels, with negligible activity on T cell K_Ca channels at concentrations up to 30 μM^[1].
UK‑78282 (100 nM; ≥2 min) hydrochloride selectively inhibits action potential firing only in striatal projection neurons of the nucleus accumbens shell in low-motivation (lowS) rats, and slows the inactivation of their A-type potassium currents; this compound reduces the amplitude of A-type potassium currents in such neurons across three groups of rats, namely low-motivation (lowS), high-motivation (highS), and moderate-motivation (midS) rats^[1].

UK‑78282 hydrochloride inhibits PHA-induced proliferation of purified human peripheral blood T cells (IC₅₀ = 2.0 μM) by acting on the late G1/early S phase of the cell cycle; it also suppresses PHA-stimulated IL‑2 production (IC₅₀ = 2.9 μM)^[1].
In Vivo:UK-78282 (1-100 nM, bilateral intracerebroventricular microinfusion, 0.5 μl per side, infusion duration 2 min + diffusion for 1 min) hydrochloride selectively enhances effort-based motivation for sucrose rewards in low-motivation Sprague-Dawley rats, with no significant effects on rats with moderate or high motivation^[2].