1. MAPK/ERK Pathway
  2. MEK

AS703026 (Synonyms: Pimasertib; MSC1936369B)

Cat. No.: HY-12042 Purity: 96.80%
Data Sheet SDS Handling Instructions

AS703026 is a highly selective, potent, ATP non-competitive allosteric inhibitor of MEK1/2, used for cancer treatment.

For research use only. We do not sell to patients.
AS703026 Chemical Structure

AS703026 Chemical Structure

CAS No. : 1236699-92-5

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $55 In-stock
5 mg $50 In-stock
10 mg $70 In-stock
50 mg $180 In-stock
100 mg $270 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Description

AS703026 is a highly selective, potent, ATP non-competitive allosteric inhibitor of MEK1/2, used for cancer treatment.

In Vitro

AS703026 (5, 0.5, and 0.1 μM) specifically blocks ERK1/2 activation in MM cells, cultured alone or with BMSCs. AS703026 inhibits the growth of MM cell lines in a dose-dependent manner, with IC50s ranging from 0.005 to 2 μM. The IC50s of AS703026 against INA-6, U266, H929 cells are 10 nM, 5 nM, 200 nM respectively. AS703026 induces apoptosis and modulates the cell cycle profile. AS703026 targets MM cells in the BM microenvironment[1]. AS703026 (10 μmol/L) inhibits ERK pathway, proliferation, and transformation in cetuximab-resistant D-MUT cells[2]. AS703026 in combination with PLX4032 significantly induces apoptosis of RPMI-7951 cells, whereas each drug used alone does not. AS703026 synergizes with small interfering RNA-mediated downregulation of BRAF to produce results similar to those of combined treatment with PLX4032 and AS703026[3].

In Vivo

AS703026 (15, 30 mg/kg) significantly inhibits the growth of tumor in the human H929 MM xenograft model in CB17 SCID mice[1]. AS703026 (10 mg/kg, p.o.) inhibits tumor growth of cetuximab-resistant tumor attributed by K-ras mutation[2].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT01378377 EMD Serono Advanced Solid Tumor June 2011 Phase 1
NCT01357330 Sanofi Solid Tumors May 2011 Phase 1
NCT00982865 Merck KGaA|Merck Serono S.A., Geneva Solid Tumors|Cancer December 2007 Phase 1
NCT01390818 EMD Serono|Sanofi Locally Advanced Solid Tumor|Metastatic Solid Tumor|Breast Cancer|Non Small Cell Lung Cancer|Melanoma|Colorectal Cancer May 2011 Phase 1
NCT01713036 Merck KGaA Locally Advanced or Metastatic Solid Tumors November 2012 Phase 1
NCT01693068 EMD Serono|Merck KGaA N-Ras Mutated Locally Advanced or Metastasis Malignant Cutaneous Melanoma December 2012 Phase 2
NCT01985191 Sanofi|Merck KGaA Neoplasm Malignant November 2013 Phase 1
NCT01992874 EMD Serono Neoplasms November 2013 Phase 1
NCT01936363 EMD Serono|Sanofi Ovarian Cancer September 2013 Phase 2
NCT01668017 Merck KGaA|Merck Serono Co., Ltd., Japan Advanced Solid Tumors|Hepatocellular Carcinoma September 2012 Phase 1
NCT00957580 EMD Serono Leukemia, Myeloid, Acute|Hematologic Neoplasms September 2009 Phase 2
NCT01085331 EMD Serono Metastatic Colorectal Cancer March 2010 Phase 1|Phase 2
NCT01016483 EMD Serono|Merck KGaA Pancreatic Adenocarcinoma November 30, 2009 Phase 1|Phase 2
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References
Preparing Stock Solutions
Concentration Volume (DMSO) 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
Cell Assay
[1]

AS703026 is dissolved in DMSO (10 mM) and stored at -20°C.

The inhibitory effects of study compounds on MM cell growth and survival are assessed by both [3H]thymidine incorporation and by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide (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 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

AS703026 is suspended in 0.5% carboxymethylcellulose (CMC)/0.25%Tween20 at 10 mg/mL.

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 AS703026 (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 using the following formula: V = 0.5 × a × b2, where “a” and “b” are the long and short diameter of the tumor, respectively. 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. AS703026 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 has not independently confirmed the accuracy of these methods. They are for reference only.

References
M.Wt

431.2

Formula

C₁₅H₁₅FIN₃O₃

CAS No.

1236699-92-5

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 96.80%

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AS703026
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HY-12042
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