Trametinib (GSK1120212)

别名: JTP-74057

Trametinib (GSK1120212, JTP-74057)是一种高特异性的,有效的MEK1/2抑制剂,无细胞试验中IC50为0.92 nM/1.8 nM,对c-Raf, B-Raf, ERK1/2没有抑制活性。Trametinib 可激活自噬并诱导凋亡。

Trametinib (GSK1120212) Chemical Structure

Trametinib (GSK1120212) Chemical Structure

CAS: 871700-17-3

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 794.43 现货
5mg RMB 647.01 现货
10mg RMB 1040.13 现货
50mg RMB 3104.01 现货
1g RMB 7944.3 现货
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客户使用Selleck的Trametinib (GSK1120212)发表文献1138

产品质控

批次: 纯度: 99.98%
99.93

常与Trametinib (GSK1120212)一起在实验中被使用的化合物

Gefitinib


Trametinib和Gefitinib联合有效抑制NRAS/KRAS/BRAF V600野生型结直肠癌(CRC)细胞增殖。


Georgiou A, et al. Mol Cancer Res. 2020 Jun;18(6):835-846.

Olaparib (AZD2281)


Trametinib和Olaparib在MESO-1/MSTO-211/H2452异种移植物和BE261T PDX模型中显示出明显更高的抗肿瘤效果。


Yang H, et al. Cell Death Discov. 2023 Feb 10;9(1):55.

Doxorubicin (DOX) HCl


Trametinib与拓扑异构酶2 (Top2)抑制剂Doxorubicin联用对K562细胞的转录组具有拮抗作用。


Mathur L, et al. Nat Commun. 2022 Aug 1;13(1):4450.

Dabrafenib


Trametinib和Dabrafenib联合治疗是FDA批准的用于恶性黑色素瘤和非小细胞肺癌(NSCLC)患者的治疗。


Brown CN, et al. Cell Signal. 2020 Jul;71:109605.

Cisplatin


Trametinib和Cisplatin联合治疗在非小细胞肺癌(NSCLC)患者中具有应用潜力。


Brown CN, et al. Cell Signal. 2020 Jul;71:109605.

Trametinib (GSK1120212)相关产品

相关信号通路图

MEK抑制剂选择性比较

细胞实验数据示例

细胞系 实验类型 给药浓度 孵育时间 活性描述 文献信息
Transitional cell carcinoma (TCC) cell lines Function assay 25 nM 6-24 h Canine TCC cell lines are sensitive to MEK inhibition 31048548
Human PDAC cell lines (MIA-PACA, PANC-1, CFPAC-1, PL45, CAPAN-2 and HPAF-II) Function assay 10 nM or 100 nM 3-days or 6-days The concentration of 10 nM trametinib consistently produced significant differences between gefitinib and trametinib alone compared to combination gefitinib and trametinib in all four sensitive cell lines (CFPAC-1, pl45, CAPAN-2 and HPAF-II). No additive effect was observed in the gefitinib insensitive or excitatory cell lines (MIA-Paca and PANC-1) 30921351
BJAB cells Function assay 0.01μM 24 h 0.01 μM trametinib effectively suppressed the ERK hyperactivation in BJAB cells caused by the combined treatment of BKM120 and Danusertib. 30947576
MDA-MB-231, SW480 and SW1116 cells Function assay 100 nM 24 h trametinib could decrease YAP levels and inhibit LMB-induced YAP upregulation in MDA-MB-231, SW1116 and SW480 cells 30833665
RG7388-resistant U87MG cells Function assay 10 nM 24 h Trametinib treatment reduced the invasive phenotype of RG7388 resistant cells. 30274984
COLO205 Growth inhibition assay 72 h IC50 = 0.001 μM ChEMBL
HT-29 Growth inhibition assay 72 h IC50 = 0.001 μM ChEMBL
COLO205 Growth inhibition assay 72 h IC50 = 0.001 μM ChEMBL
MV522 Growth inhibition assay 72 h IC50 = 0.001 μM ChEMBL
HT-29 Growth inhibition assay 72 h IC50 = 0.002 μM ChEMBL
MV522 Growth inhibition assay 72 h IC50 = 0.002 μM ChEMBL
NCI-H727 Growth inhibition assay 72 h IC50 = 0.002 μM ChEMBL
NCI-H727 Growth inhibition assay 72 h IC50 = 0.002 μM ChEMBL
SW1417 Growth inhibition assay 72 h IC50 = 0.003 μM ChEMBL
SW1417 Growth inhibition assay 72 h IC50 = 0.003 μM ChEMBL
Calu6 Growth inhibition assay 72 h IC50 = 0.003 μM ChEMBL
LS1034 Growth inhibition assay 72 h IC50 = 0.004 μM ChEMBL
SW1463 Growth inhibition assay 72 h IC50 = 0.004 μM ChEMBL
SW1463 Growth inhibition assay 72 h IC50 = 0.004 μM ChEMBL
Calu6 Growth inhibition assay 72 h IC50 = 0.004 μM ChEMBL
LS1034 Growth inhibition assay 72 h IC50 = 0.005 μM ChEMBL
RKO Growth inhibition assay 72 h IC50 = 0.005 μM ChEMBL
NCI-H508 Growth inhibition assay 72 h IC50 = 0.008 μM ChEMBL
KM12 Growth inhibition assay 72 h IC50 = 0.01 μM ChEMBL
A427 Growth inhibition assay 72 h IC50 = 0.01 μM ChEMBL
NCI-H1155 Growth inhibition assay 72 h IC50 = 0.01 μM ChEMBL
HCT8 Growth inhibition assay 72 h IC50 = 0.014 μM ChEMBL
MDA-MB-175-VII Growth inhibition assay 72 h IC50 = 0.016 μM ChEMBL
A549 Growth inhibition assay 72 h IC50 = 0.016 μM ChEMBL
RKO Growth inhibition assay 72 h IC50 = 0.018 μM ChEMBL
NCI-H23 Growth inhibition assay 72 h IC50 = 0.02 μM ChEMBL
A427 Growth inhibition assay 72 h IC50 = 0.022 μM ChEMBL
KM12 Growth inhibition assay 72 h IC50 = 0.023 μM ChEMBL
NCI-H508 Growth inhibition assay 72 h IC50 = 0.023 μM ChEMBL
MDA-MB-231 Growth inhibition assay 3 days GI50 = 0.025 μM ChEMBL
SW837 Growth inhibition assay 72 h IC50 = 0.025 μM ChEMBL
SW480 Growth inhibition assay 72 h IC50 = 0.026 μM ChEMBL
NCI-H1355 Growth inhibition assay 72 h IC50 = 0.027 μM ChEMBL
NCI-H23 Growth inhibition assay 72 h IC50 = 0.029 μM ChEMBL
EFM19 Growth inhibition assay 72 h IC50 = 0.03 μM ChEMBL
T84 Growth inhibition assay 72 h IC50 = 0.03 μM ChEMBL
A549 Growth inhibition assay 72 h IC50 = 0.034 μM ChEMBL
NCI-H1792 Growth inhibition assay 72 h IC50 = 0.035 μM ChEMBL
SW480 Growth inhibition assay 72 h IC50 = 0.037 μM ChEMBL
COR-L23 Growth inhibition assay 72 h IC50 = 0.037 μM ChEMBL
SW1573 Growth inhibition assay 72 h IC50 = 0.038 μM ChEMBL
Calu3 Growth inhibition assay 72 h IC50 = 0.039 μM ChEMBL
HCC827 Growth inhibition assay 72 h IC50 = 0.04 μM ChEMBL
HOP62 Growth inhibition assay 72 h IC50 = 0.05 μM ChEMBL
NCI-H1355 Growth inhibition assay 72 h IC50 = 0.052 μM ChEMBL
NCI-H1792 Growth inhibition assay 72 h IC50 = 0.053 μM ChEMBL
HCT8 Growth inhibition assay 72 h IC50 = 0.055 μM ChEMBL
T84 Growth inhibition assay 72 h IC50 = 0.061 μM ChEMBL
SW900 Growth inhibition assay 72 h IC50 = 0.072 μM ChEMBL
SW837 Growth inhibition assay 72 h IC50 = 0.074 μM ChEMBL
DLD1 Growth inhibition assay 72 h IC50 = 0.093 μM ChEMBL
MDA-MB-175-VII Growth inhibition assay 72 h IC50 = 0.096 μM ChEMBL
SW900 Growth inhibition assay 72 h IC50 = 0.127 μM ChEMBL
Calu3 Growth inhibition assay 72 h IC50 = 0.158 μM ChEMBL
COR-L23 Growth inhibition assay 72 h IC50 = 0.329 μM ChEMBL
DLD1 Growth inhibition assay 72 h IC50 = 0.632 μM ChEMBL
点击查看更多细胞系数据

生物活性

产品描述 Trametinib (GSK1120212, JTP-74057)是一种高特异性的,有效的MEK1/2抑制剂,无细胞试验中IC50为0.92 nM/1.8 nM,对c-Raf, B-Raf, ERK1/2没有抑制活性。Trametinib 可激活自噬并诱导凋亡。
特性 药效大于PD0325901或AZD6244
靶点
MEK1 [1]
(Cell-free assay)
MEK2 [1]
(Cell-free assay)
0.92 nM 1.8 nM
体外研究(In Vitro)
体外研究活性

GSK1120212抑制 MBP 的磷酸化,对于不同亚型的Raf和MEK 而言,IC50在0.92 nM-3.4 nM。GSK1120212对c-Raf, B-Raf, ERK1和ERK2的激酶活性没有抑制作用。另外,GSK1120212对于其它98种激酶没有很强的抑制作用。GSK1120212对于人结肠癌细胞系有很强的抑制作用,其中HT-29和COLO205细胞组成型表达有活性的B-Raf突变,这两种细胞对GSK1120212最为敏感,IC50分别是0.48 nM 和 0.52 nM。含有k-Raf突变的细胞系对GSK1120212的敏感性介于如下范围,IC50是2.2-174 nM. 相反地,COLO320 DM细胞中B-Raf 和K-Ras均为野生型,因而即便在10 μM都对GSK1120212有抗性。用GSK1120212处理24小时可以诱导所有敏感细胞的细胞周期停滞在G1期。与此一致,GSK1120212处理使得大部分人结肠癌细胞系中p15INK4b 和/或p27KIP1的表达量上升。GSK1120212能诱导HT-29和COLO205细胞的凋亡,COLO205细胞更为敏感。[1] GSK1120212抑制外周血单核细胞产生肿瘤坏死因子-α和白介素-6。 [2]

激酶实验 Raf-MEK-ERK级联激酶检测
非磷酸化的髓鞘碱性蛋白(MBP)涂覆到ELISA板上,B-Raf/c-Raf的活性形式与非磷酸化MEK1/MEK2和ERERK2混合在10 μM ATP和12.5 mM MgCl2,其MOPS缓冲液中含有不同浓度的GSK1120212。 MBP的磷酸化是由抗磷酸化的MBP抗体进行检测。
细胞实验 细胞系 HT-29, HCT-15, HCT116, COLO205, LS-174T, SW480, SW620, T84, LoVo和COLO320
浓度 溶解在DMSO中至终浓度约10 μM
孵育时间 3天或4天
方法

指数生长的细胞预培养在96孔组织培养板中24小时后用GSK1120212孵育。细胞生长是通过体外毒理学测定试剂盒(基于磺酰罗丹明B)检测。对于细胞凋亡测定,漂浮和贴壁细胞被收集并用70%乙醇固定。用PBS洗涤后,将细重胞悬在100微克/毫升RNA酶和25微克/毫升的碘化丙啶(PI)中,至于37℃黑暗中30分钟。每一个单细胞的DNA含量是用流式细胞仪Cytomics FC500或番石榴EasyCyte来确定。

实验图片 检测方法 检测指标 实验图片 PMID
Western blot ERRα / IDH3 / c-Myc / Cyclin D1 pERK /ERK / pS6 / S6 β-catenin 30185207
Growth inhibition assay Cell proliferation MTT assay 30185207
Immunofluorescence phospho-PR(S345) β-catenin 29237804
体内研究(In Vivo)
体内研究活性

按0.3 mg/kg或1 mg/kg 的剂量口服GSK1120212(一天一次共14天)能有效抑制HT-29肿瘤,1 mg/kg 的剂量可完全抑制肿瘤生长。在癌症组织中,一次口服1 mg/kg GSK1120212能完全抑制ERK1/2的磷酸化,14天后能提高p15INK4b和p27KIP1的表达量。在COLO205肿瘤模型中,0.3 mg/kg剂量的GSK1120212就足以抑制肿瘤生长,1 mg/kg剂量的GSK1120212可以使2/3的老鼠的肿瘤消退至可检测水平之下。[1] 0.1 mg/kg剂量的GSK1120212完全抑制佐剂性关节炎(AIA)和II型胶原诱导的关节炎(CIA) Lewis大鼠或DBA1/J小鼠。[2]

动物实验 Animal Models 雌雄BALB/c-nu/nu小鼠皮下注射HT-29或COLO205细胞
Dosages 1 mg/kg/day
Administration 口服
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05275374 Not yet recruiting
Cancer|BRAF V600 Mutation|Melanoma|Colorectal Cancer|Thyroid Cancer|Nonsmall Cell Lung Cancer
Xynomic Pharmaceuticals Inc.
December 2023 Phase 1|Phase 2
NCT06098872 Not yet recruiting
Arteriovenous Malformations
University Health Network Toronto
November 2023 Phase 2
NCT05907304 Recruiting
Advanced or Metastatic Solid Tumors
Erasca Inc.
August 17 2023 Phase 1
NCT05874414 Recruiting
Cholangiocarcinoma
Genfit
August 21 2023 Phase 1|Phase 2

化学信息&溶解度

分子量 615.39 分子式

C26H23FIN5O4

CAS号 871700-17-3 SDF Download Trametinib (GSK1120212) SDF
Smiles CC1=C2C(=C(N(C1=O)C)NC3=C(C=C(C=C3)I)F)C(=O)N(C(=O)N2C4=CC=CC(=C4)NC(=O)C)C5CC5
储存条件(自收到货起)

体外溶解度
批次:

DMSO : 8 mg/mL ( 12.99 mM; DMSO吸湿会降低化合物溶解度,请使用新开封DMSO)

Water : Insoluble

Ethanol : Insoluble

摩尔浓度计算器

体内溶解度
批次:

现配现用,请按从左到右的顺序依次添加,澄清后再加入下一溶剂

动物体内配方计算器

实验计算

摩尔浓度计算器

质量 浓度 体积 分子量

动物体内配方计算器(澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)

mg/kg g μL

第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)

% DMSO % % Tween 80 % ddH2O
%DMSO %

计算结果:

工作液浓度: mg/ml;

DMSO母液配制方法: mg 药物溶于μL DMSO溶液(母液浓度mg/mL,:如该浓度超过该批次药物DMSO溶解度,请先联系Selleck);

体内配方配制方法:μL DMSO母液,加入μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入μL ddH2O,混匀澄清。

体内配方配制方法:μL DMSO母液,加入μL Corn oil,混匀澄清。

注意:1. 首先保证母液是澄清的;
2.一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。

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常见问题及建议解决方法

问题 1:
Could you help us with the best way to prepare Trametinib for in vivo i.p. injections?

回答:
S2673 can be dissovled in 4% DMSO/corn oil at 3 mg/ml clearly.

问题 2:
How to solve the problem that this product didn't dissolve up to 10mM in DMSO at room temperature?

回答:
The solution can be heated up to 50 degree to help dissolve. Besides, sonication (with a probe sonicator) also helped greatly.

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