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Reagenzien und Instrumente für die Immunologie Zellbiologie und Molekularbiologie

Pimasertib [1236699-92-5]

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Katalog-Nummer HY-12042-10mg

Size : 10mg

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Telefonnummer : +1 850 650 7790

Marke : MedChemExpress

Contact local distributor :

Telefonnummer : +1 850 650 7790

Pimasertib (AS703026) is a highly selective, ATP non-competitive allosteric orally available MEK1/2 inhibitor.

Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.

Pimasertib Chemische Struktur

CAS. Nr. : 1236699-92-5

This product is a controlled substance and not for sale in your territory.

Based on 6 publication(s) in Google Scholar

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Alle Isoformen anzeigen

Beschreibung

Pimasertib (AS703026) is a highly selective, ATP non-competitive allosteric orally available MEK1/2 inhibitor^[1]^[2].

IC₅₀ & Target^[1]

MEK1

MEK2

In Vitro

Pimasertib (5, 0.5, and 0.1 μM) specifically blocks ERK1/2 activation in MM cells, cultured alone or with BMSCs. Pimasertib inhibits the growth of MM cell lines in a dose-dependent manner, with IC₅₀s ranging from 0.005 to 2 μM. The IC₅₀s of Pimasertib against INA-6, U266, H929 cells are 10 nM, 5 nM, 200 nM respectively. Pimasertib induces apoptosis and modulates the cell cycle profile. Pimasertib targets MM cells in the BM microenvironment^[1]. Pimasertib (10 μmol/L) inhibits ERK pathway, proliferation, and transformation in cetuximab-resistant D-MUT cells^[2]. Pimasertib in combination with PLX4032 significantly induces apoptosis of RPMI-7951 cells, whereas each drug used alone does not. Pimasertib synergizes with small interfering RNA-mediated downregulation of BRAF to produce results similar to those of combined treatment with PLX4032 and Pimasertib^[3].

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

In Vivo

Pimasertib (15, 30 mg/kg) significantly inhibits the growth of tumor in the human H929 MM xenograft model in CB17 SCID mice^[1]. Pimasertib (10 mg/kg, p.o.) inhibits tumor growth of cetuximab-resistant tumor attributed by K-ras mutation^[2].

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

Klinische Studie

Molekulargewicht

431.20

Formel

C₁₅H₁₅FIN₃O₃

CAS. Nr.

1236699-92-5

Appearance

Solid

Color

Light yellow to khaki

SMILES

FC1=C(C=CC(I)=C1)NC2=CN=CC=C2C(NC[C@@H](CO)O)=O

Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

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

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : ≥ 100 mg/mL (231.91 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.3191 mL	11.5955 mL	23.1911 mL
5 mM	0.4638 mL	2.3191 mL	4.6382 mL
10 mM	0.2319 mL	1.1596 mL	2.3191 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molaritätsrechner
Verdünnungsrechner

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

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: ≥ 2.5 mg/mL (5.80 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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: ≥ 2.5 mg/mL (5.80 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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: ≥ 2.5 mg/mL (5.80 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 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 (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(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.

Reinheit & Dokumentation

Purity: 99.88%

Select Batch:

Data Sheet (282 KB) SDS (252 KB)

COA (251 KB) LCMS (267 KB)

Handling Instructions (2659 KB)

Verweise

[1]. Kim K, et al. Blockade of the MEK/ERK signalling cascade by AS703026, a novel selective MEK1/2 inhibitor, induces pleiotropic anti-myeloma activity in vitro and in vivo. Br J Haematol, 2010, 149(4), 537-549. [Content Brief]

[2]. Park SJ, et al. The MEK1/2 inhibitor AS703026 circumvents resistance to the BRAF inhibitor PLX4032 in human malignant melanoma cells. Am J Med Sci. 2013 Dec;346(6):494-8. [Content Brief]

[3]. Yoon J, et al. MEK1/2 inhibitors AS703026 and AZD6244 may be potential therapies for KRAS mutated colorectal cancer that is resistant to EGFR monoclonal antibody therapy. Cancer Res, 2011, 71(2), 445-453. [Content Brief]

Zellassay ^[1]	The inhibitory effects of study compounds on MM cell growth and survival are assessed by both [³H]thymidine incorporation and by measuring MTT dye absorbance. Cells (10⁴/well for MM cell line, in triplicates and 2-5×10⁵/well for patient MM cells) are cultured in 96-well plates for 3 days (MM cell lines) or 5-days (patient MM cells). For the [³H]thymidine incorporation assay, cells are pulsed with 0.5 μCi (0.0185 MBq)/well [³H]thymidine for 6 h (cell lines), harvested onto glass fiber filters, and counted in a β-scintillation counter. Due to low DNA synthesis of patient MM cells, they are pulsed with 2 μCi/well [³H]thymidine and measured during the last 36 h of culture. MCE hat die Genauigkeit dieser Methoden nicht unabhängig bestätigt. Sie dienen nur als Referenz.
Tierverwaltung ^[1]	CB17 severe combined immunodeficiency (SCID) mice are subcutaneously inoculated with H929 (4×10⁶) cells in 100 μL RPMI-1640 medium. Mice developed palpable tumors (appr 130 mm³) approximately 3 weeks after cell injection and are randomized to receive orally twice daily either Pimasertib (15 or 30 mg/kg) or control vehicle alone. Tumor size is measured every other day in 2 dimensions using calipers, and tumor volume is calculated. Animals are euthanized when their tumors reach 2 cm³ in volume, when they are moribund or show paralysis or major compromise in their quality of life occurs. Tumor formation changes in mice treated with control vehicle vs. Pimasertib are plotted using the GraphPad Prism version 4.03 for Windows. Tumors are subjected to immunoblotting and immunochemistry analyses using specific monoclonal (m)Abs. Images are examined with a Leica DM LB research microscope, captured using Leica IM50 Image Manager, and processed using Adobe Photoshop Software version 7.0. MCE hat die Genauigkeit dieser Methoden nicht unabhängig bestätigt. Sie dienen nur als Referenz.
Verweise	[1]. Kim K, et al. Blockade of the MEK/ERK signalling cascade by AS703026, a novel selective MEK1/2 inhibitor, induces pleiotropic anti-myeloma activity in vitro and in vivo. Br J Haematol, 2010, 149(4), 537-549. [Content Brief] [2]. Park SJ, et al. The MEK1/2 inhibitor AS703026 circumvents resistance to the BRAF inhibitor PLX4032 in human malignant melanoma cells. Am J Med Sci. 2013 Dec;346(6):494-8. [Content Brief] [3]. Yoon J, et al. MEK1/2 inhibitors AS703026 and AZD6244 may be potential therapies for KRAS mutated colorectal cancer that is resistant to EGFR monoclonal antibody therapy. Cancer Res, 2011, 71(2), 445-453. [Content Brief]

Complete Stock Solution Preparation Table

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

DMSO	1 mM	2.3191 mL	11.5955 mL	23.1911 mL	57.9777 mL
	5 mM	0.4638 mL	2.3191 mL	4.6382 mL	11.5955 mL
	10 mM	0.2319 mL	1.1596 mL	2.3191 mL	5.7978 mL
	15 mM	0.1546 mL	0.7730 mL	1.5461 mL	3.8652 mL
	20 mM	0.1160 mL	0.5798 mL	1.1596 mL	2.8989 mL
	25 mM	0.0928 mL	0.4638 mL	0.9276 mL	2.3191 mL
	30 mM	0.0773 mL	0.3865 mL	0.7730 mL	1.9326 mL
	40 mM	0.0580 mL	0.2899 mL	0.5798 mL	1.4494 mL
	50 mM	0.0464 mL	0.2319 mL	0.4638 mL	1.1596 mL
	60 mM	0.0387 mL	0.1933 mL	0.3865 mL	0.9663 mL
	80 mM	0.0290 mL	0.1449 mL	0.2899 mL	0.7247 mL
	100 mM	0.0232 mL	0.1160 mL	0.2319 mL	0.5798 mL

Pimasertib [1236699-92-5]

Katalog-Nummer HY-12042-10mg

Contact local distributor :

Marke : MedChemExpress

Contact local distributor :

Alle MEK Isoform-spezifische Produkte anzeigen:

Molaritätsrechner

Verdünnungsrechner

Complete Stock Solution Preparation Table

Pimasertib Related Classifications

Keywords:

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Pimasertib [1236699-92-5]

Katalog-Nummer HY-12042-10mg

Contact local distributor :

Marke : MedChemExpress

Contact local distributor :

Alle MEK Isoform-spezifische Produkte anzeigen:

Pimasertib Related Antibodies

Molaritätsrechner

Verdünnungsrechner

Complete Stock Solution Preparation Table

Pimasertib Related Classifications

Keywords:

Sie könnten auch an folgenden Produkten interessiert sein: