Trametinib

Trametinib (GSK1120212; JTP-74057) is an orally active MEK inhibitor that inhibits MEK1 and MEK2 with IC₅₀s of about 2 nM. Trametinib activates autophagy and induces apoptosis, cross the blood-brain barrier (BBB), used in research related to subarachnoid hemorrhage (SAH)^[1][2]. IC50 & Target:IC50: 2 nM (MEK1/2)^[1] In Vitro: Trametinib (GSK1120212;JTP-74057) (0.1-100 nM) blocks tumor necrosis factor-α and interleukin-6 production from peripheral blood mononuclear cells (PBMCs). Trametinib (JTP-74057) inhibits the growth of 9 out of 10 human colorectal cancer cell lines, and they shows cell-cycle arrest at the G1 phase after drug tratment^[1].
The combination of GSK2118436 and Trametinib (GSK1120212) effectively inhibits cell growth, decreases ERK phosphorylation, decreases cyclin D1 protein, and increases p27(kip1) protein in the resistant clones^[2]. In Vivo: Adjuvant-induced arthritis (AIA) and type II collageninduced arthritis (CIA) development are suppressed almost completely by 0.1 mg/kg of Trametinib (GSK1120212; JTP-74057) or 10 mg/kg of HWA486^[1].
Trametinib (0.3 mg/kg, 1 mg/kg, p.o.) is effective in inhibiting the HT-29 xenograft growth in a nude mouse xenograft model^[2].
In a female Sprague-Dawley rat model of experimental subarachnoid hemorrhage (SAH) induced by autologous blood injection into the prechiasmatic cistern, trametinib (0.5 mg/kg, intraperitoneal injection, administered at 3, 9, and 24 hours after SAH induction) regulates cerebrovascular contractile function, significantly reduces the contractile response of the basilar artery to endothelin ET-1, decreases the maximum contractile amplitude of the middle cerebral artery to 5-CT, alleviates elevated intracranial pressure (ICP) in the subacute phase, improves neurological outcomes, and enhances overall health status without significant adverse effects^[6].