Cayman TRAM-34

TRAM-34 is a membrane-permeable inhibitor of the intermediate-conductance calcium-activated potassium channel (IKCa1/K_Ca3.1).¹ It blocks IKCa1 (K_ds = 20 and 25 nM for the cloned and native channel in COS-7 cells and human T lymphocytes, respectively) with 200- to 1,500-fold selectivity for IKCa1 over K_v (K_v1.1-K_v1.5, K_v3.1, K_v4.2), K_IR2.1, BK/K_Ca1.1, SK_Ca (rSK_Ca2, hSK_Ca2, hSK_Ca3), native SK_Ca/K_Ca2, and CRAC in Jurkat T cells, as well as sodium and chloride channels. It also inhibits nonselective lysophosphatidylcholine-induced cation currents (IC₅₀ = 38 nM).² TRAM-34 suppresses reactivation of human-derived T lymphocytes stimulated with anti-CD3 antibody after an initial pretreatment to upregulate IKCa1 channels (mean EC₅₀s = 295 and 910 nM from sensitive and less sensitive human donors, respectively).¹ It does not reduce viability of human T lymphocytes at a concentration of 5 μM over 48 hours incubation. In vitro, TRAM-34 (10-40 μM) inhibits proliferation of human endometrial cancer cells and induces cell cycle arrest at the g₀/g₁ phase.³ It also inhibits proliferation of LNCaP and PC3 prostate cancer cells and proliferation induced by epidermal growth factor (EGF) in smooth muscle A7r5 cells (IC₅₀ = 8 nM).^4,5 In vivo, TRAM-34 (120 mg/kg per day) reduces intimal hyperplasia by approximately 40% after 1, 2, and 6 weeks in a rat model of balloon catheter injury. TRAM-34 (30 μM) treatment of HEC-1-A cells prior to flank implantation into nude mice slows tumor growth in vivo.

WARNING This product is not for human or veterinary use.