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.

1. Wulff, H., Miller, M.J., Hänsel, W., et al. Design of a potent and selective inhibitor of the intermediate-conductance Ca²⁺-activated K⁺ channel, IKCa1: A potential immunosuppressant. Proc. Natl. Acad. Sci. USA 97(14), 8151-8156 (2000).

2. Schilling, T., and Eder, C. TRAM-34 inhibits nonselective cation channels. Pflugers Arch. 454(4), 559-563 (2007).

3. Wang, Z.H., Shen, B., Yao, H.L., et al. Blockage of intermediate-conductance-Ca(2+) -activated K(+) channels inhibits progression of human endometrial cancer. Oncogene 26(35), 5107-5114 (2007).

4. Lallet-Daher, H., Roudbaraki, M., Bavencoffe, A., et al. Intermediate-conductance Ca²⁺-activated K⁺ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry. Oncogene 28(15), 1792-1806 (2009).

5. Köhler, R., Wulff, H., Eichler, I., et al. Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis. Circulation 108(9), 1119-1125 (2003).