Trimebutine 

Trimebutine is a multi-target inhibitor and opioid receptor agonist with antimuscarinic activity. Trimebutine inhibits L-type Ca²⁺ channels and large-conductance calcium-activated potassium channels (BK_Ca channels), thereby inhibiting extracellular calcium influx and potassium ion efflux. Trimebutine also targets Toll-like receptors, inhibits Toll-like receptor 2/4/7/8/9 signals, and inhibits LPS-induced IRAK1 activation, as well as ERK1/2, JNK and NF-κB activation, thereby exerting anti-inflammatory effects. Trimebutine also induces tumor cell apoptosis by inhibiting the AKT/ERK pathway. Trimebutine also inhibits excessive contraction of smooth muscle and can be used in the study of gastrointestinal disorders such as irritable bowel syndrome (IBS)^{[1][2][3][4][5][6]}.

Trimebutine (0-1000 μM; 48 h) significantly inhibits the viability of SHG44, U251, and U-87 MG glioma cells, with IC₅₀ of 98.28 μM, 128.27 μM, and 204.06 μM, respectively, and has low toxicity to normal HEB cells^[1].
Trimebutine (0-200 μM; 24-72 h) inhibits the migration of U-87 MG cells in a concentration- and time-dependent manner^[1].
Trimebutine (0-200 μM; 48-72 h) induces apoptosis in glioma cells, downregulates Bcl-2, upregulates Bax and activates Caspase-3, while inhibiting the phosphorylation of AKT (Ser473) and ERK (Thr202/Tyr204)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Trimebutine (100 mg/kg/day; intraperitoneal injection; once a day; 7 days) inhibits tumor growth in the subcutaneous xenograft model of U-87 MG glioma in female nude mice, increases TUNEL-positive apoptotic cells in tumor tissues, downregulates Bcl-2, upregulated Bax, and inhibits p-AKT and p-ERK signaling pathways^[1].
Trimebutine (50 mg/kg; oral; single dose) significantly reduces pain response at 60 mmHg pressure in the colorectal distension model of male mice after 4 hours of treatment, exhibits weaker overall effect than GIC-1001 (HY-B0380B) at an equimolar dose^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

387.47

C₂₂H₂₉NO₅

39133-31-8

Solid

White to off-white

O=C(OCC(C1=CC=CC=C1)(N(C)C)CC)C2=CC(OC)=C(OC)C(OC)=C2

Room temperature in continental US; may vary elsewhere.

4°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Fan YP, et al. Trimebutine Promotes Glioma Cell Apoptosis as a Potential Anti-tumor Agent. Front Pharmacol. 2018 Jun 21;9:664.  [Content Brief]

  [2]. Cenac N, et al. A novel orally administered trimebutine compound (GIC-1001) is anti-nociceptive and features peripheral opioid agonistic activity and Hydrogen Sulphide-releasing capacity in mice. Eur J Pain. 2016 May;20(5):723-30.  [Content Brief]

  [3]. Long Y, et al. Effectiveness of trimebutine maleate on modulating intestinal hypercontractility in a mouse model of postinfectious irritable bowel syndrome. Eur J Pharmacol. 2010 Jun 25;636(1-3):159-65.  [Content Brief]

  [4]. Tan W, et al. Effects of trimebutine maleate on colonic motility through Ca²+-activated K+ channels and L-type Ca²+ channels. Arch Pharm Res. 2011 Jun;34(6):979-85.  [Content Brief]

  [5]. Xu J, et al. Trimebutine, a small molecule mimetic agonist of adhesion molecule L1, contributes to functional recovery after spinal cord injury in mice. Dis Model Mech. 2017 Sep 1;10(9):1117-1128.  [Content Brief]

  [6]. Ogawa N, et al. Trimebutine suppresses Toll-like receptor 2/4/7/8/9 signaling pathways in macrophages. Arch Biochem Biophys. 2021 Oct 30;711:109029.  [Content Brief]