TRAM-34

TRAM-34 is a membrane-permeable inhibitor of the intermediate-conductance calcium-activated potassium channel (IKCa1/KCa3.1). It blocks IKCa1 (Kds = 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 Kv (Kv1.1-Kv1.5, Kv3.1, Kv4.2), Kir2.1, BK/KCa1.1, SKCa (rSKCa2, hSKCa2, hSKCa3), native SKCa/KCa2, and CRAC in Jurkat T cells, as well as sodium and chloride channels. It also inhibits nonselective lysophosphatidylcholine-induced cation currents (IC50 = 38 nM). 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). 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. 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). 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.Formal Name: 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole. CAS Number: 289905-88-0. Molecular Formula: C22H17ClN2. Formula Weight: 344.8. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 0.5 mg/ml, DMSO: 0.5 mg/ml, Ethanol: 0.2 mg/ml. SMILES: ClC(C=CC=C1)=C1C(C2=CC=CC=C2)(C3=CC=CC=C3)N4C=CC=N4. InChi Code: InChI=1S/C22H17ClN2/c23-21-15-8-7-14-20(21)22(25-17-9-16-24-25,18-10-3-1-4-11-18)19-12-5-2-6-13-19/h1-17H. InChi Key: KBFUQFVFYYBHBT-UHFFFAOYSA-N.