| 包装 | 价格(元) |
| 10mM (in 1mL DMSO) | 电议 |
| 50mg | 电议 |
| 200mg | 电议 |
| 500mg | 电议 |
Preparation Method | Two micrograms of dephosphorylated MBP (Upstate) in 0.2 M sodium carbonate (pH 9.4) was coated onto 96-well plates at 4 !ムovernight. After blocking with 1% BSA, the inactive forms of MEK1 (2 ng) or MEK2 (4 ng) with inactive ERK2 (50 ng) diluted in assay buffer were preincubated in the plates with test compoundsGBP¨including Trametinib (GSK1120212)GBP(C)at room temperature for 10 min. The kinase reaction was started by the addition of active B-Raf (V599E) or c-Raf, with 10 M ATP and 12.5 mM MgCl2. After incubation at 30 C for 30 min, the phosphorylation of MBP by ERK2 was detected with peroxidase-labeled antiphosphorylated MBP antibody. |
Reaction Conditions | Trametinib (GSK1120212) with protein at room temperature for 10 minutes |
Applications | Trametinib (GSK1120212) binds specifically to MEK1/2.IC50 in cell-free assay was 0.92 nM/1.8 nM. |
Cell lines | HT-29 cells |
Preparation Method | Cells were precultured for 24 h and then exposed to JTP-70902. After incubation with Trametinib (GSK1120212) for 4 days, cell viability was assessed using Cell Counting Kit-8. |
Reaction Conditions | 0-1000nM Trametinib (GSK1120212) for 4 days |
Applications | Trametinib (GSK1120212), identified as a potent p15INKb inducer, modulates p27KIP1, cyclin D1, cyclin A and c-Myc protein levels and induces G1 arrest in HT-29 cells. |
Animal models | Trametinib (GSK1120212) in the nude mouse HT-29 xenograft model |
Preparation Method | HT-29 cells were inoculated subcutaneously into the right flank of nude mice, and Trametinib (GSK1120212) was administered orally twice daily for 21 days starting from 5 days after the inoculation. |
Dosage form | 10-100mg/kg Trametinib (GSK1120212) twice daily for 21 days |
Applications | Tumor growth was significantly suppressed in mice treated with 100 mg/kg Trametinib (GSK1120212) during the course of the treatment. |
| 半岛bd体育手机客户端 描述 | Trametinib (GSK1120212, JTP-74057) is a second-generation small molecule inhibitor of MEK kinase. It functions as allosteric, ATP noncompetitive inhibitor with nanomolar activity against both MEK 1 and MEK 2 kinases with IC50 is 0.7-14.9 nM for MEK1/MEK2[3,7]. Trametinib (GSK1120212), identified as a potent p15INKb inducer, modulates p27KIP1, cyclin D1, cyclin A and c-Myc protein levels and induces G1 arrest in HT-29 cells[2]. Trametinib (GSK1120212) blocked tumor necrosis factor-α and interleukin-6 production from PBMCs. AIA and CIA development were suppressed almost completely by 0.1 mg/kg of JTP-74057 or 10 mg/kg of leflunomide. In the CIA, Trametinib (GSK1120212), but not leflunomide, suppressed collagen-reactive T-cell proliferation ex vivo[1]. Among the different cell lines evaluated in the study, those with either BRAFV600E mutation or activating mutations in KRAS or NRAS were the most sensitive.Trametinib (GSK1120212) inhibited the MEK1/2-dependent activating dual phosphorylation of ERK1/2 on both T202 and Y204[4]. In xenograft models of HT-29 and COLO205 colorectal tumor cell lines, trametinib demonstrated robust anticancer activity when administered daily for 14 days, Tumor growth was significantly suppressed in mice treated with 100 mg/kg Trametinib (GSK1120212) during the course of the treatment, by single oral dosing of 100 mg/kg Trametinib (GSK1120212), the phosphorylation of ERK1/2 in the established tumor tissues was completely inhibited, and both p15INK4b and p27KIP1 mRNA levels were upregulated in parallel[2,5]. In patients treated with Trametinib (GSK1120212)for malignant melanoma most common adverse events observed were rash, diarrhea, peripheral edema, fatigue, and dermatitis acneiform[6]. References: |
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