TRAM-34

製品コードS1160 バッチS116001

印刷

化学情報

Chemical Structure Synonyms Triarylmethane-34 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C22H17ClN2
分子量 344.84 CAS No. 289905-88-0
Solubility (25°C)* 体外 cyclohexane 8 mg/mL (23.19 mM)
DMSO 0.4 mg/mL (1.15 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
in vitro Unlike clotrimazole, TRAM-34 selectively inhibits IKCa1 without blocking cytochrome P450 enzyme (CYP3A4). TRAM-34 potently inhibits cloned IKCa1 channel in IKCa1-transfected COS-7 cells as well as native IKCa 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. TRAM-34 exhibits 200- to 1,500-fold selectivity over other ion channels such as KV, BKCa, SKCa, Na+, CRAC and Cl- channels. TRAM-34 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. TRAM-34 (5 μM) does not inhibit cell viability of human T lymphocytes or several cell lines. [1] TRAM-34 significantly inhibits EGF-induced IKCa1 up-regulation, and EGF-stimulated proliferation of A7r5 cells with IC50 of 8 nM. [2] TRAM-34 treatment inhibits proliferation of human endometrial cancer (EC) cells, and blocks EC cell cycle at G0/G1 phase. [3] Inhibition of the IKCa1 channel by TRAM-34 (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. [4]
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. [1] Administration of TRAM-34 at 120 mg/kg/day significantly reduces intimal hyperplasia by ~40% in a rat model of balloon catheter injury (BCI). [2] Consistent with its in vitro role in inhibiting the proliferation of EC cells, TRAM-34 treatment at 30 μM slows the development of HEC-1-A tumor in vivo. [3]
特徴 Has a therapeutic profile similar to clotrimazole, but TRAM-34 has a superior safety profile.

プロトコル(参考用のみ)

キナーゼアッセイ 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 TRAM-34 taken as a measure of channel block.
細胞アッセイ 細胞株 Human T lymphocytes, Jurkat E6-1, MEL, C2F3, CHO, COS-7, L929, NGP, NLF, and RBL-2H3
濃度 Dissolved in DMSO, final concentration ~10 μM
反応時間 48 hours
実験の流れ Cells are exposed to TRAM-34 for 48 hours. After 48 hours, cells are harvested by suction (suspension cells) or by trypsinization (adherent cell lines), centrifuged, resuspended in 0.5 mL PBS containing 1 μg/mL propidium iodide (PI), and red fluorescence measured on a FACScan flow cytometer. The percentage of dead cells is determined by their PI uptake, 104 cells of every sample being analyzed.
動物実験 動物モデル Sprague-Dawley rats subjected to BCI of the left CA by use of a 2F Fogarty embolectomy catheter
投薬量 120 mg/kg/day
投与方法 Subcutaneous injection

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Aggressive migration in acidic pH of a glioblastoma cancer stem cell line in vitro is independent of ASIC and KCa3.1 ion channels, but involves phosphoinositide 3-kinase [ Pflugers Arch, 2023, 475(3):405-416] PubMed: 36522586
Dextran sodium sulfate potentiates NLRP3 inflammasome activation by modulating the KCa3.1 potassium channel in a mouse model of colitis [ Cell Mol Immunol, 2022, 19(8):925-943] PubMed: 35799057
Targeting the KCa3.1 channel suppresses diabetes-associated atherosclerosis via the STAT3/CD36 axis [ Diabetes Res Clin Pract, 2022, S0168-8227(22)00588-5] PubMed: 35149165
KCNN4 induces multiple chemoresistance in breast cancer by regulating BCL2A1 [ Am J Cancer Res, 2020, 10(10):3302-3315] PubMed: 33163271

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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