HY-50706-100mg | Selumetinib [606143-52-6] Clinisciences

Description

Selumetinib (AZD6244) is selective, non-ATP-competitive oral MEK1/2 inhibitor, with an IC₅₀ of 14 nM for MEK1. Selumetinib (AZD6244) inhibits ERK1/2 phosphorylation.

IC₅₀ & Target^[3]^[4]

MEK

12 nM (IC₅₀)

MEK1

14 nM (IC₅₀)

MEK2

Cellular Effect

Cell Line	Type	Value	Description	References
A-375	IC₅₀	31 nM Compound: AZD6244	Antiproliferative activity against human A375 cells expressing BRAF V600E mutant after 72 hrs by Cell titer-glo assay Antiproliferative activity against human A375 cells expressing BRAF V600E mutant after 72 hrs by Cell titer-glo assay	[PMID: 23474388]
A549	IC₅₀	> 100 μM Compound: AZD6244	Antiproliferative activity against human A549 cells after 48 hrs by MTT assay Antiproliferative activity against human A549 cells after 48 hrs by MTT assay	[PMID: 30777660]
ASPC1	IC₅₀	64.2 nM Compound: AZD6244; AZD	Antiproliferative activity against human AsPC1 cells harboring KRAS G12D mutant after 72 hrs by CellTiter-Glo assay Antiproliferative activity against human AsPC1 cells harboring KRAS G12D mutant after 72 hrs by CellTiter-Glo assay	[PMID: 28038940]
BaF3	IC₅₀	> 1 x 10^-4 nM Compound: AZD6244; AZD	Antiproliferative activity against mouse BA/F3 cells harboring KRAS G12D mutant after 72 hrs in presence of IL-3 by CellTiter-Glo assay Antiproliferative activity against mouse BA/F3 cells harboring KRAS G12D mutant after 72 hrs in presence of IL-3 by CellTiter-Glo assay	[PMID: 28038940]
BaF3	IC₅₀	100 nM Compound: AZD6244; AZD	Antiproliferative activity against mouse BA/F3 cells harboring KRAS G12D mutant after 72 hrs by CellTiter-Glo assay Antiproliferative activity against mouse BA/F3 cells harboring KRAS G12D mutant after 72 hrs by CellTiter-Glo assay	[PMID: 28038940]
COLO 205	IC₅₀	59 nM Compound: AZD6244	Antiproliferative activity against human COLO205 cells harboring BRAF mutant/wild type KRAS/wild type PIK3CA after 72 hrs by CCK8 assay Antiproliferative activity against human COLO205 cells harboring BRAF mutant/wild type KRAS/wild type PIK3CA after 72 hrs by CCK8 assay	[PMID: 29317148]
DLD-1	IC₅₀	1.25 μM Compound: 41	Anticancer activity against human DLD-1 cells assessed as reduction in cell viability incubated for 24 hrs by Cell Titer-Glo assay Anticancer activity against human DLD-1 cells assessed as reduction in cell viability incubated for 24 hrs by Cell Titer-Glo assay	[PMID: 33445154]
HCT-116	IC₅₀	0.95 μM Compound: 41	Anticancer activity against human HCT-116 cells assessed as reduction in cell viability incubated for 24 hrs by Cell Titer-Glo assay Anticancer activity against human HCT-116 cells assessed as reduction in cell viability incubated for 24 hrs by Cell Titer-Glo assay	[PMID: 33445154]
PANC-1	IC₅₀	> 1 x 10^-4 nM Compound: AZD6244; AZD	Antiproliferative activity against human PANC1 cells harboring KRAS G12D mutant after 72 hrs by CellTiter-Glo assay Antiproliferative activity against human PANC1 cells harboring KRAS G12D mutant after 72 hrs by CellTiter-Glo assay	[PMID: 28038940]
SK-CO-1	IC₅₀	117 nM Compound: AZD6244; AZD	Antiproliferative activity against human SKCO1 cells harboring KRAS G12V mutant after 72 hrs by CellTiter-Glo assay Antiproliferative activity against human SKCO1 cells harboring KRAS G12V mutant after 72 hrs by CellTiter-Glo assay	[PMID: 28038940]
SW480	IC₅₀	0.422 μM Compound: AZD6244	Antiproliferative activity against human SW480 cells after 72 hrs by MTT assay Antiproliferative activity against human SW480 cells after 72 hrs by MTT assay	[PMID: 27448918]
SW-620	IC₅₀	15 nM Compound: AZD6244; AZD	Antiproliferative activity against human SW620 cells harboring KRAS G12V mutant after 72 hrs by CellTiter-Glo assay Antiproliferative activity against human SW620 cells harboring KRAS G12V mutant after 72 hrs by CellTiter-Glo assay	[PMID: 28038940]

In Vitro

Selumetinib (AZD6244) causes a time- and dose-dependent reduction in DNA synthesis and cell viability in primary, induces growth arrest and apoptosis associated with the inactivation of ERK in primary 2-1318 cells^[1].
Selumetinib (AZD6244) (1μM) shows anti-proliferative effects through G0/G1 arrest on H-441, H-1437 cells^[2].
Selumetinib (AZD6244) results in the growth inhibition of several cell lines containing B-Raf and Ras mutations but has no effect on a normal fibroblast cell line^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Selumetinib (AZD6244, 50 and 100 mg/kg, p.o.) decreases the growth rate of 4-1318 xenografts in a dose-dependent manner; AZD6244 when given at the dose of 50 mg/kg also significantly suppresses the growth of the 5-1318, 2-1318, 26-1004, and 29-1104 xenografts^[1]. Selumetinib (ARRY-142886, 10, 25, 50, or 100 mg/kg, p.o.) is capable of inhibiting both ERK1/2 phosphorylation and growth of HT-29 xenograft tumors in nude mice. Tumor regressions are also seen in a BxPC3 xenograft model^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Essai clinique

Masse moléculaire

457.68

Formule

C₁₇H₁₅BrClFN₄O₃

CAS No.

606143-52-6

Appearance

Solid

Color

White to off-white

SMILES

O=C(C1=C(C(F)=C2N=CN(C2=C1)C)NC3=CC=C(C=C3Cl)Br)NOCCO

Livraison

Room temperature in continental US; may vary elsewhere.

Stockage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	1 year
	-20°C	6 months

Solvant et solubilité

In Vitro:

DMSO : 20.83 mg/mL (45.51 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H₂O : < 0.1 mg/mL (insoluble)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.1849 mL	10.9247 mL	21.8493 mL
5 mM	0.4370 mL	2.1849 mL	4.3699 mL
10 mM	0.2185 mL	1.0925 mL	2.1849 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

Calculateur de molarité
Calculateur de dilution

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 1 mg/mL (2.18 mM); Clear solution

This protocol yields a clear solution of ≥ 1 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (10.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 1 mg/mL (2.18 mM); Clear solution

This protocol yields a clear solution of ≥ 1 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (10.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 1 mg/mL (2.18 mM); Clear solution

This protocol yields a clear solution of ≥ 1 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (10.0 mg/mL) to 900 μL Corn oil, and mix evenly.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 50% PEG300 50% Saline
Solubility: 10 mg/mL (21.85 mM); Suspended solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

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mg/kg

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(per animal)

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(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Pureté et documentation

Purity: 99.87%

Select Batch:

SDS (393 KB)

COA (252 KB) HNMR (193 KB) LCMS (408 KB)

Instruction de manipulation (2659 KB)

Références

[1]. Huynh H, et al, Targeted inhibition of the extracellular signal-regulated kinase kinase pathway with AZD6244 (ARRY-142886) in the treatment of hepatocellular carcinoma. Mol Cancer Therapy, 2007, 6 (1), 138-146 [Content Brief]

[2]. Garon EB, et al. Identification of common predictive markers of in vitro response to the Mek inhibitor selumetinib (AZD6244; ARRY-142886) in human breast cancer and non-small cell lung cancer cell lines. Mol Cancer Thera, 2010, 9 (7), 1985-1994. [Content Brief]

[3]. Yeh TC, et al. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin Cancer Res, 2007, 13 (5), 1576-1583. [Content Brief]

[4]. Sebolt-Leopold JS, et al. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer. 2004 Dec;4(12):937-47. [Content Brief]

[5]. Dela Cruz FS, et al. A case study of an integrative genomic and experimental therapeutic approach for rare tumors: identification of vulnerabilities in a pediatric poorly differentiated carcinoma. Genome Med. 2016 Oct 31;8(1):116. [Content Brief]

[6]. Weisberg E, et al. Upregulation of IGF1R by mutant RAS in leukemia and potentiation of RAS signaling inhibitors by small-molecule inhibition of IGF1R. Clin Cancer Res. 2014 Nov 1;20(21):5483-95. [Content Brief]

Essai de kinase ^[3]	The activity of MEK1 is assessed by measuring the incorporation of [γ-³³P]phosphate from [γ-³³P]ATP onto ERK2. The assay is carried out in a 96-well polypropylene plate with an incubation mixture (100 μL) composed of 25 mM HEPES (pH 7.4), 10 mM MgCl₂, 5 mM β-glycerolphosphate, 100 μM sodium orthovanadate, 5 mM DTT, 5 nM MEK1, 1 μM ERK2, and 0 to 80 nM selumetinib (final concentration of 1% DMSO). The reactions are initiated by the addition of 10 μM ATP (with 0.5 μC k[γ-³³P]ATP/well) and incubated at room temperature for 45 min. An equal volume of 25% trichloracetic acid is added to stop the reaction and precipitate the proteins. Precipitated proteins are trapped onto glass fiber B filter plates, excess labeled ATP is washed off with 0.5% phosphoric acid, and radioactivity is counted in a liquid scintillation counter. ATP dependence is determined by varying the amount of ATP in the reaction mixture. MCE n'a pas confirmé de manière indépendante l'exactitude de ces méthodes. Ils sont pour référence seulement.
Test cellulaire ^[1]	Primary HCC cells are plated at a density of 2.0×10⁴ per well in growth medium. After 48 h in growth medium, the cell monolayer is rinsed twice with MEM. Cells are treated with various concentrations of Selumetinib (AZD6244, 0, 0.5, 1.0, 2.0, 3.0, and 4.0 μM) for 24 or 48 h. Cell viability is determined by the MTT assay. Cell proliferation is assayed using a bromodeoxyuridine kit as described by the manufacturer. Experiments are repeated at least thrice, and the data are expressed as mean±SE. MCE n'a pas confirmé de manière indépendante l'exactitude de ces méthodes. Ils sont pour référence seulement.
Administration animale ^[1]	To investigate the effects of Selumetinib (AZD6244) on HCC xenografts, AZD6244 is suspended in water at an appropriate concentration. Mice bearing HCC xenografts are p.o. given, twice a day, with either 100 μL of water (n=12) or 50 mg (n=12) or 100 mg (n=12) of AZD6244 per kilogram of body weight for 21 days, starting from day 7 after tumor implantation. Growth of established tumor xenografts is monitored at least twice weekly by Vernier caliper measurement of the length (a) and width (b) of the tumor. Tumor volume is calculated as (a × b²)/2. Animals are sacrificed 3 h after the last dose of ADZ6244, and body and tumor weights are recorded, with the tumors harvested for analysis. MCE n'a pas confirmé de manière indépendante l'exactitude de ces méthodes. Ils sont pour référence seulement.
Références	[1]. Huynh H, et al, Targeted inhibition of the extracellular signal-regulated kinase kinase pathway with AZD6244 (ARRY-142886) in the treatment of hepatocellular carcinoma. Mol Cancer Therapy, 2007, 6 (1), 138-146 [Content Brief] [2]. Garon EB, et al. Identification of common predictive markers of in vitro response to the Mek inhibitor selumetinib (AZD6244; ARRY-142886) in human breast cancer and non-small cell lung cancer cell lines. Mol Cancer Thera, 2010, 9 (7), 1985-1994. [Content Brief] [3]. Yeh TC, et al. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin Cancer Res, 2007, 13 (5), 1576-1583. [Content Brief] [4]. Sebolt-Leopold JS, et al. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer. 2004 Dec;4(12):937-47. [Content Brief] [5]. Dela Cruz FS, et al. A case study of an integrative genomic and experimental therapeutic approach for rare tumors: identification of vulnerabilities in a pediatric poorly differentiated carcinoma. Genome Med. 2016 Oct 31;8(1):116. [Content Brief] [6]. Weisberg E, et al. Upregulation of IGF1R by mutant RAS in leukemia and potentiation of RAS signaling inhibitors by small-molecule inhibition of IGF1R. Clin Cancer Res. 2014 Nov 1;20(21):5483-95. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.1849 mL	10.9247 mL	21.8493 mL	54.6233 mL
	5 mM	0.4370 mL	2.1849 mL	4.3699 mL	10.9247 mL
	10 mM	0.2185 mL	1.0925 mL	2.1849 mL	5.4623 mL
	15 mM	0.1457 mL	0.7283 mL	1.4566 mL	3.6416 mL
	20 mM	0.1092 mL	0.5462 mL	1.0925 mL	2.7312 mL
	25 mM	0.0874 mL	0.4370 mL	0.8740 mL	2.1849 mL
	30 mM	0.0728 mL	0.3642 mL	0.7283 mL	1.8208 mL
	40 mM	0.0546 mL	0.2731 mL	0.5462 mL	1.3656 mL

Selumetinib Related Classifications

MAPK/ERK Pathway Apoptosis
MEK Apoptosis

Selumetinib [606143-52-6]

Cat# HY-50706-100mg

Contatta il distributore locale :

Marca : MedChemExpress

Contatta il distributore locale :

Other Forms of Selumetinib:

Voir tous les produits spécifiques à Isoform MEK:

Calculateur de molarité

Calculateur de dilution

Complete Stock Solution Preparation Table

Selumetinib Related Classifications

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Selumetinib [606143-52-6]

Cat# HY-50706-100mg

Contatta il distributore locale :

Marca : MedChemExpress

Contatta il distributore locale :

Other Forms of Selumetinib:

Voir tous les produits spécifiques à Isoform MEK:

Selumetinib Related Antibodies

Calculateur de molarité

Calculateur de dilution

Complete Stock Solution Preparation Table

Selumetinib Related Classifications

Keywords:

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