Name: Trametinib (GSK1120212)
Brand: Selleck Chemicals
SKU: S2673
Rating: 5 (1326 reviews)

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Control de calidad (Quality Control)

Lote: Pureza: 99.98%

99.98

Dianas relacionadas	ERK p38 MAPK Raf JNK Ras KRas S6 Kinase MAP4K TAK1 Mixed Lineage Kinase
Otros MEK Inhibidores	PD0325901 (Mirdametinib) U0126-EtOH PD 98059 CI-1040 (PD184352) (E/Z)-BIX02189 Pimasertib (AS-703026) Refametinib (RDEA119) TAK-733 AZD8330 GDC-0623

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Líneas celulares	Tipo de ensayo	Concentración	Tiempo de incubación	Formulación	Descripción de la actividad	PMID
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	DMSO	Trametinib treatment reduced the invasive phenotype of RG7388 resistant cells.	30274984
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
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
Transitional cell carcinoma (TCC) cell lines	Function assay	25 nM	6-24 h		Canine TCC cell lines are sensitive to MEK inhibition	31048548
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
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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	615.39	Fórmula	C₂₆H₂₃FIN₅O₄	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	871700-17-3	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	JTP-74057			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

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 8 mg/mL (12.99 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Water : Insoluble

Ethanol : Insoluble

Calculadora de Molaridad

Masa	Concentración	Volumen	Peso molecular
=	×	×

Calculadora de Dilución Calculadora de Peso Molecular

In vivo Lote:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

Dosis: mg/kg Peso promedio de los animales: g Volumen de dosificación por animal:μL Número de animales:

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH₂O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción (Mechanism of Action)

Características	More potent than PD0325901 or AZD6244.
Targets/IC₅₀/Ki	MEK1 (Cell-free assay) 0.92 nM MEK2 (Cell-free assay) 1.8 nM
In vitro	Trametinib (GSK1120212) inhibits the phosphorylation of MBP regardless of the isotype of Raf and MEK, with IC50 ranging from 0.92 nM to 3.4 nM. It demonstrates no inhibition of the kinase activities of c-Raf, B-Raf, ERK1 and ERK2. In addition, this compound does not show drastic inhibitory activity against the other 98 kinases. It displays potent inhibitory activity against human colorectal cancer cell lines. HT-29 and COLO205 cells, which are known to have a constitutively active B-Raf mutant, are most sensitive to it with IC50 0.48 nM and 0.52 nM, respectively. The cell lines bearing a K-Ras mutation show a wide range of sensitivity to it with IC50 of 2.2-174 nM. In contrast, COLO320 DM cells, bearing the wild-type gene in both B-Raf and K-Ras, are found to be resistant even at 10 μM. Treatment for 24 hours induces cell-cycle arrest at the G1 phase in all sensitive cell lines. Consistently, it leads to upregulation of p15^INK4b and/or p27^KIP1 in most of the colorectal cancer cell lines. It inhibits constitutive ERK phosphorylation in all sensitive cell lines. This compound induces apoptosis both in HT-29 and COLO205 cells, but that COLO205 cells are more sensitive than HT-29 cells in terms of apoptosis induction. It blocks tumor necrosis factor-α and interleukin-6 production from peripheral blood mononuclear cells (PBMCs).
Ensayo de quinasa	Ensayo de quinasa en cascada Raf-MEK-ERK
Ensayo de quinasa	La proteína básica de mielina no fosforilada (MBP) se recubre en una placa de ELISA, y la forma activa de B-Raf/c-Raf se mezcla con MEK1/MEK2 no fosforilada y ERERK2 en 10 μM de ATP y 12,5 mM de MgCl₂ que contiene tampón MOPS en presencia de varias concentraciones de Trametinib (GSK1120212). La fosforilación de MBP se detecta mediante el anticuerpo anti-fosfo-MBP.
In vivo	Oral administration of Trametinib (GSK1120212) at 0.3 mg/kg or 1 mg/kg once daily for 14 days is effective in inhibiting the HT-29 xenograft growth, and 1 mg/kg of this compound almost completely blocks the tumor increase. The phosphorylation of ERK1/2 is completely inhibited in the established tumor tissues by single oral dose of 1 mg/kg, and both p15^INK4b and p27^KIP1 protein levels are upregulated after 14 days of treatment. In the COLO205 xenograft model, tumor regression is observed even at a dose of 0.3 mg/kg. At a dose of 1 mg/kg, a complete regression is obtained in 4 out of 6 mice in which the tumor degenerates to the point that tumor volume is not measurable. Administration at 0.1 mg/kg almost completely suppresses adjuvant-induced arthritis (AIA) and type II collagen-induced arthritis (CIA) in Lewis rats or DBA1/J mice, respectively.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/21523318/ [2] https://pubmed.ncbi.nlm.nih.gov/22245957/ [3] https://pubmed.ncbi.nlm.nih.gov/22389471/ [4] https://pubmed.ncbi.nlm.nih.gov/22733540/

Aplicaciones (Applications)

Métodos	Biomarcadores	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

Información del ensayo clínico (Clinical Trial Information)

(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
NCT05275374	Not yet recruiting	Cancer\|BRAF V600 Mutation\|Melanoma\|Colorectal Cancer\|Thyroid Cancer\|Nonsmall Cell Lung Cancer	Xynomic Pharmaceuticals Inc.	December 2024	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

Preguntas frecuentes (Frequently Asked Questions)

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

Respuesta:
It can be dissolved in 4% DMSO/corn oil at 3 mg/ml clearly.

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

Respuesta:
The solution can be heated up to 50 degrees to help dissolve it. Besides, sonication (with a probe sonicator) also greatly helps with this compound.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Trametinib (GSK1120212) MEK inhibitor

Estructura química

Peso molecular: 615.39

Control de calidad (Quality Control)

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Solubilidad (Solubility)

Calculadora de Molaridad

Calculadora de formulación in vivo (Solución clara)

Mecanismo de acción (Mechanism of Action)

Aplicaciones (Applications)

Información del ensayo clínico (Clinical Trial Information)

Preguntas frecuentes (Frequently Asked Questions)

Trametinib (GSK1120212) MEK inhibitor

Estructura química

Peso molecular: 615.39

Control de calidad (Quality Control)

Cultivo celular, tratamiento y concentración de trabajo (Cell Culture, Treatment & Working Concentration)

Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Solubilidad (Solubility)

Calculadora de Molaridad

Calculadora de formulación in vivo (Solución clara)

Mecanismo de acción (Mechanism of Action)

Aplicaciones (Applications)

Información del ensayo clínico (Clinical Trial Information)

Preguntas frecuentes (Frequently Asked Questions)

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)