TRAM-34 is a selective and potent inhibitor of the intermediate-conductance Ca2+-activated K+ channel (IKCa1, KCa3.1) with Kd of 20 nM. Unlike clotrimazole, TRAM-34 dose not inhibit mammalian cytochrome P450 enzyme (CYP3A4). TRAM-34 displays >200-fold selectivity for IKCa1 over Kv, BKCa, SKCa, Na, CRAC, and chloride channels. TRAM-34 does not exhibit toxicity against a variety of cell lines in vitro or cause obvious deleterious changes in a limited short-term acute toxicity study in rodents. TRAM-34 significantly inhibits the reactivation process of human lymphocytes by mitogenic stimuli, and when in combination with cyclosporin A suppresses T-cell mitogenesis more potently than either compound alone. TRAM-34 significantly inhibits EGF-induced IKCa1 up-regulation, and EGF-stimulated proliferation of A7r5 cells. TRAM-34 treatment at 120 mg/kg/day significantly reduces intimal hyperplasia in rat model of balloon catheter injury (BCI). TRAM-34 inhibits human endometrial cancer (EC) cell proliferation, arrests its cell cycle at G0/G1 phase, and suppresses the development of EC tumors in nude mice. By specifically targeting IKCa1, TRAM-34 treatment inhibits the prostate cancer (PCa) cell proliferation in a dose-dependent manner, involving growth arrest and an accumulation of p21Cip1.
| Cell Experiment | |
|---|---|
| Cell lines | Human T lymphocytes, Jurkat E6-1, MEL, C2F3, CHO, COS-7, L929, NGP, NLF, and RBL-2H3 |
| Preparation method | Exposing cells to TRAM-34 for 48 hours. 48 hours later , 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 measured red fluorescence on a FACScan flow cytometer. The percentage of dead cells is determined by their PI uptake, 104 cells of every sample being analyzed. |
| Concentrations | Dissolved in DMSO, final concentration ~10 μM |
| Incubation time | 48 hours |
| Animal Experiment | |
|---|---|
| Animal models | Sprague-Dawley rats subjected to BCI of the left CA by use of a 2F Fogarty embolectomy catheter |
| Formulation | Formulated in peanut oil |
| Dosages | 120 mg/kg/day |
| Administration | Subcutaneous injection |
| Molecular Weight | 344.84 |
| Formula | C22H17ClN2 |
| CAS Number | 289905-88-0 |
| Solubility (25°C) | DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
[5] Tom Schilling, et al. TRAM-34 inhibits nonselective cation channels
| Related Potassium Channel Products |
|---|
| NPBA
NPBA is a potassium K2P channel TASK-3 (KCNK9) agonist and a tandem pore domain weak inward rectifier K+ channel (TWIK2) channel blocker. In addition, NPBA inhibits the activation of NLRP3 inflammasome in macrophages. |
| BeKm-1
BeKm-1 is a HERG (human ether-a-go-go-related gene) blocking compound. |
| Apamin
Apamin (Apamine) is a specifically selective blocker of Ca2+-activated K+ (SK) channels and exhibits anti-inflammatory and anti-fibrotic activity. |
| Phe-Met-Arg-Phe amide trifluoroacetate
Phe-Met-Arg-Phe amide trifluoroacetate is an activator of K+ current, with ED50 of 23 nM in the peptidergic caudodorsal neurons. |
| Iberiotoxin
Iberiotoxin is a toxin isolated from Buthus tamulus scorpion venom. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
