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TRAM-34 Potassium Channel inhibitor

Cat.No.S1160

TRAM-34 (Triarylmethane-34) is a selective and potent inhibitor of the intermediate-conductance Ca2+-activated K+ channel (IKCa1, KCa3.1) with Kd of 20 nM, 200- to 1500-fold selective over other ion channels, and does not block cytochrome P450.
TRAM-34 Potassium Channel inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 344.84

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Quality Control

Batch: Purity: 99.98%
99.98

Solubility

In vitro
Batch:

cyclohexane : 8 mg/mL

DMSO : 0.4 mg/mL (1.15 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

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In vivo
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Chemical Information, Storage & Stability

Molecular Weight 344.84 Formula

C22H17ClN2

 Storage (From the date of receipt)
CAS No. 289905-88-0 Download SDF Storage of Stock Solutions

Synonyms Triarylmethane-34 Smiles C1=CC=C(C=C1)C(C2=CC=CC=C2)(C3=CC=CC=C3Cl)N4C=CC=N4

Mechanism of Action

Features
Has a therapeutic profile similar to clotrimazole, but TRAM-34 has a superior safety profile.
Targets/IC50/Ki
IKCa1 (KCa3.1)
20 nM(Kd)
In vitro
Unlike clotrimazole, TRAM-34 selectively inhibits IKCa1 without blocking cytochrome P450 enzyme (CYP3A4). This compound potently inhibits cloned IKCa1 channel in IKCa1-transfected COS-7 cells as well as native IK currents in human T lymphocytes and T84 cells with Kd of 20 nM, 25 nM, and 22 nM, respectively, more potently than clotrimazole with Kd of 70 nM, 100 nM, and 90 nM, respectively. It exhibits 200- to 1,500-fold selectivity over other ion channels such as KV, BKCa, SKCa, Na+, CRAC and Cl- channels. This chemical significantly inhibits anti-CD3 Ab or PKC-activator PMA plus calcium-ionophore ionomycin induced activation of human T lymphocytes with IC50 of 295-910 nM and 85-830 nM, respectively. It (5 μM) does not inhibit cell viability of human T lymphocytes or several cell lines. This compound significantly inhibits EGF-induced IKCa1 up-regulation, and EGF-stimulated proliferation of A7r5 cells with IC50 of 8 nM. This chemical treatment inhibits proliferation of human endometrial cancer (EC) cells, and blocks EC cell cycle at G0/G1 phase. Inhibition of the IKCa1 channel by this compound (1-30 μM) leads to dose-dependent suppression of the proliferation but not apoptosis of LNCaP and PC-3 prostate cancer (PCa) cells, involving an increase of p21Cip1 and cell arrest in the G1 cycle.
Kinase Assay
Electrophysiology
The human IKCa1 is cloned and expressed in COS-7 cells. Cells are studied in the whole-cell configuration of the patch-clamp technique. The holding potential is 280 mV. The internal pipette solution contains: 145 mM K+ aspartate, 2 mM MgCl2, 10 mM Hepes, 10 mM K2EGTA, and 8.5 mM CaCl2 (1 μM free Ca2+), pH 7.2, 290-310 mOsm. To reduce currents from the native chloride channels in COS-7 cells, Na+ aspartate Ringer is used as an external solution: 160 mM Na+ aspartatey/4.5 mM KCl/2 mM CaCl2/1 mM MgCl2/5 mM Hepes, pH 7.4/290-310 mOsm. IKCa currents in COS-7 cells are elicited by 200-ms voltage ramps from -120 mV to 40 mV applied every 10 seconds and the reduction of slope conductance at -80 mV by this compound taken as a measure of channel block.
In vivo
TRAM-34 treatment at ~500-1,000 times the channel-blocking dose (0.5 mg/kg/day) for 7 days is nontoxic to mice. Administration of this compound at 120 mg/kg/day significantly reduces intimal hyperplasia by ~40% in a rat model of balloon catheter injury (BCI). Consistent with its in vitro role in inhibiting the proliferation of EC cells, this chemical treatment at 30 μM slows the development of HEC-1-A tumor in vivo.
References
  • [4] https://pubmed.ncbi.nlm.nih.gov/19270724/

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