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Trametinib

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Chemical Structure| 871700-17-3 同义名 : JTP-74057;GSK1120212;Trametinib. Brand name: Mekinist.;GSK 1120212 GSK1120212
CAS号 : 871700-17-3
货号 : A188937
分子式 : C26H23FIN5O4
纯度 : 99%+
分子量 : 615.395
MDL号 : MFCD17215075
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(40.62 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 2 mg/mL clear

PO 0.5% CMC-Na 30 mg/mL suspension

生物活性
靶点

  • MEK2

    MEK2, IC50:1.8 nM

  • MEK1

    MEK1, IC50:0.92 nM
描述 Trametinib, also called as GSK1120212 or JTP-74057, can strongly inhibit MEK1/2 kinase activities with IC50 value of 0.92nM and 1.8nM, respectively, without inhibition on the other 98 kinases (measured by Raf-MEK-ERK cascade kinase assay) regardless of the isotype of Raf and MEK. Trametinib can inhibit constitutive ERK phosphorylation (downstream of MEK) in cell lines, while the effect on anti-proliferation differs. Among them, HT-29 and COLO205 cells with a constitutively active B-Raf mutant were most sensitive to trametinib while COLO320 DM cells bearing the wild-type gene in both B-Raf and K-Ras were found to be resistant to trametinib. Oral treatment of trametinib 1mg/kg daily for 14 days blocked the tumor increase almost completely in nude mice bearing the HT-29 xenografts[1].Trametinib is indicated for the treatment in patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations detected by an FDA-approved test[2].
作用机制 Trametinib binds to MEK1/2 and induces allosteric inhibition of MEK1/2 catalysis.[3]
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT03225664 Lung Diseases Due to External ... 展开 >>Agents Non-Small Cell Lung Cancer 收起 << Phase 1 Phase 2 Recruiting May 2020 United States, Texas ... 展开 >> University of Texas MD Anderson Cancer Center Recruiting Houston, Texas, United States, 77030 Contact: Clinical Research Operations       CR_Study_Registration@mdanderson.org 收起 <<
NCT02872259 Melanoma Phase 1 Phase 2 Recruiting March 2020 Norway ... 展开 >> Haukeland University Hospital Recruiting Bergen, Norway, 5021 Contact: Oddbjørn Straume, MD, PhD       oddbjorn.straume@helse-bergen.no    Akershus Univerisity Hospital Not yet recruiting Lørenskog, Norway, 1478 Contact: Jürgen Geisler, MD, PhD       Jurgen.geisler@ahus.no    Oslo University Hospital, Radiumhospitalet Recruiting Oslo, Norway, 0424 Contact: Marta Nyakas, MD, PhD       marta.nyakas@ous.no    University Hospital of North Norway Recruiting Tromsø, Norway, 9038 Contact: Anita Amundsen, MD       Anita.amundsen@unn.no    St. Olavs Hospital Recruiting Trondheim, Norway, 7006 Contact: Jarle Karlsen, MD       Jarle.Karlsen@stolav.no 收起 <<
NCT02039947 Melanoma and Brain Metastases Phase 2 Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.62mL

0.33mL

0.16mL

8.12mL

1.62mL

0.81mL

16.25mL

3.25mL

1.62mL
参考文献

[1]Fujishita T, Kajino-Sakamoto R, et al. Antitumor activity of the MEK inhibitor trametinib on intestinal polyp formation in Apc(Δ716) mice involves stromal COX-2. Cancer Sci. 2015 Jun;106(6):692-9.

[2]Kawaguchi K, Igarashi K, et al. MEK inhibitors cobimetinib and trametinib, regressed a gemcitabine-resistant pancreatic-cancer patient-derived orthotopic xenograft (PDOX). Oncotarget. 2017 Jul 18;8(29):47490-47496.

[3]Walters DM, Lindberg JM, et al. Inhibition of the growth of patient-derived pancreatic cancer xenografts with the MEK inhibitor trametinib is augmented by combined treatment with the epidermal growth factor receptor/HER2 inhibitor lapatinib. Neoplasia. 2013;15(2):143-55.

[4]Ganesh S, Shui X, et al. β-Catenin mRNA Silencing and MEK Inhibition Display Synergistic Efficacy in Preclinical Tumor Models. Mol Cancer Ther. 2018;17(2):544-553.