TRAM-34

  CAY-23385-10 10 mg

Data Sheet:     SDS:    

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289905-88-0  

A crystalline solid  

≥98%  

344,8  

-20  

-20  

1460  

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Description

 

TRAM-34 is a membrane-permeable inhibitor of the intermediate-conductance calcium-activated potassium channel (IKCa1/KCa3.1).{41340} 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).{41342} 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).{41340} 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.{41343} 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).{41344,41341} 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.

 

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