| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Pimasertib (formerly SAR-245509, AS-703026, MSC-1936369B) is a selective, orally bioavailable, non-ATP competitive (allosteric), and MEK1/2 inhibitor with potential anticancer activity. It inhibits MEK1/2 in MM cell lines with IC50 values of 5 nM to 2 M. In a human plasmacytoma xenograft model using H929 MM cells, it exhibits significant in vitro anti-proliferative activity as well as significant in vivo antitumor efficacy.
| Targets |
MEK1; MEK2
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| ln Vitro |
Pimasertib (5, 0.5, and 0.1 μM) specifically inhibits ERK1/2 activation in MM cells that are cultured alone or with BMSCs. Pimasertib's IC50 values, which range from 0.005 to 2 M, show that it inhibits the growth of MM cell lines in a dose-dependent manner. Pimasertib has IC50 values of 10 nM, 5 nM, and 200 nM for INA-6, U266, and H929 cells, respectively. Both apoptosis and the cell cycle profile are modified by pimasertib. The BM microenvironment is the target of pimasertib's action on MM cells[1]. In D-MUT cells that are resistant to cetuximab, pimasertib (10 mol/L) inhibits ERK pathway, proliferation, and transformation[2]. In contrast to each drug used alone, pimasertib significantly increases the likelihood that RPMI-7951 cells will undergo apoptosis when combined with PLX4032. To achieve outcomes comparable to those of PLX4032 and Pimasertib combined therapy, Pimasertib works in synergy with small interfering RNA-mediated downregulation of BRAF[3].
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| ln Vivo |
Pimasertib (15, 30 mg/kg) significantly slows tumor growth in CB17 SCID mice bearing a human H929 MM xenograft[1]. Pimasertib (10 mg/kg, p.o.) inhibits the growth of tumors that are resistant to cetuximab due to a mutation in the K-ras gene[2].
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| Enzyme Assay |
AS703026 is dissolved in 2.5% DMSO. Activated diphosphorylated MEK (pp-MEK) assays contained 40 M 33P-γATP (AppKm 8.5 MμM, 0.5 nM human-activated MEK1 or MEK2, and 1 M kinase-dead ERK2 (AppKm 0.73 μM). All tests are conducted in a buffer containing 20 mM HEPES (pH 7.2), 5 mM 2-mercaptoethanol, 0.15 mg/mL BSA, and 10 mM MgCl2. For all assays, the final 33P- ATP concentration is 0.02 μCi/μL. After 40 minutes, pp-MEK kinase reactions are halted by transferring 30 μL of the reaction mixture to Durapore 0.45-μm filters plates containing 12.5% TCA. Filters are dried before being read on a TopCount using liquid scintilant. For IC50, concentration response data are examined. The IC50 of initially unphosphorylated MEK (u-MEK) is calculated by preincubating 0.2 nM recombinant human MEK1 or MEK2 with vehicle or with AS703026 for 40 minutes in reaction buffer. By adding a final concentration of 20 nM B-RafV600E and 30 μM ATP for 10 minutes, phosphorylation/activation is started. The B-Raf inhibitor SB590885 is then added (final concentration 100 nM), quenching B-Raf activity, and the MEK kinase activity is measured by adding 1 μM KD-ERK2 and 0.02 μCi/μL 33P-ATP in reaction buffer. By transferring 30μL of the reaction mixture to a Durapore filter plate and reading as usual, the kinase reactions are stopped after 90 minutes.
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| Cell Assay |
Both [3H]thymidine incorporation and MTT dye absorbance measurements are used to determine the inhibitory effects of study compounds on MM cell growth and survival. In 96-well plates, cells are cultured for 3 days (MM cell lines) or 5 days (patient MM cells) at a density of 104 cells per well in triplicates and 2-5×105 cells per well. 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 the patient's MM cells' low DNA synthesis, they are pulsed with 2 μCi/well [3H]thymidine and their DNA synthesis is measured over the last 36 hours of culture.
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| Animal Protocol |
H929 (4×106 cells) are subcutaneously injected into CB17 severe combined immunodeficiency (SCID) mice in 100 μL RPMI-1640 medium. Pimasertib (15 or 30 mg/kg) or the control vehicle alone was administered orally twice daily to the mice, which had palpable tumors (about 130 mm3) by the third week after cell injection. Every other day, calipers are used to measure the tumor's size in two dimensions, and the tumor's volume is computed. When an animal's quality of life is significantly compromised, its tumors grow to a volume of 2 cm3, it becomes moribund, it exhibits paralysis, or it becomes moribund. GraphPad Prism version 4.03 for Windows is used to plot changes in tumor formation in mice treated with control medication vs. pimasertib. Utilizing specific monoclonal (m) antibodies, immunoblotting and immunochemistry analyses of tumors are performed. Abs. Leica IM50 Image Manager is used to take pictures, Leica DM LB research microscope is used for image analysis, and Adobe Photoshop Software 7.0 is used for post-processing.
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| References |
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| Molecular Formula |
C15H15FIN3O3
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|---|---|
| Molecular Weight |
431.20
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| Exact Mass |
431.01
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| Elemental Analysis |
C, 41.78; H, 3.51; F, 4.41; I, 29.43; N, 9.74; O, 11.13
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| CAS # |
1236699-92-5
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| Related CAS # |
1236361-78-6 (HCl); 1236699-92-5;
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| Appearance |
Solid powder
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| SMILES |
C1=CC(=C(C=C1I)F)NC2=C(C=CN=C2)C(=O)NC[C@@H](CO)O
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| InChi Key |
VIUAUNHCRHHYNE-JTQLQIEISA-N
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| InChi Code |
InChI=1S/C15H15FIN3O3/c16-12-5-9(17)1-2-13(12)20-14-7-18-4-3-11(14)15(23)19-6-10(22)8-21/h1-5,7,10,20-22H,6,8H2,(H,19,23)/t10-/m0/s1
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| Chemical Name |
N-[(2S)-2,3-dihydroxypropyl]-3-(2-fluoro-4-iodoanilino)pyridine-4-carboxamide
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| Synonyms |
MSC 1936369B; SAR 245509; AS-703026; SAR245509; SAR-245509; AS703026; AS 703026
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.80 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.80 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 0.5% CMC+0.25% Tween 80: 30mg/mL |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04789668 | Active Recruiting |
Drug: Pimasertib Drug: Bintrafusp Alfa |
Stage IV Lung Cancer AJCC v8 Metastatic Melanoma |
M.D. Anderson Cancer Center | January 15, 2021 | Phase 1 Phase 2 |
| NCT04985604 | Recruiting | Drug: Tovorafenib Drug: Pimasertib |
Melanoma Solid Tumor |
Day One Biopharmaceuticals, Inc. | July 15, 2021 | Phase 1 Phase 2 |
| NCT01985191 | Completed | Drug: Pimasertib Drug: SAR405838 |
Neoplasm Malignant | Sanofi | November 2013 | Phase 1 |
| NCT01992874 | Completed | Drug: Pimasertib Capsule (Part A) Drug: Pimasertib Tablet (Part A) |
Neoplasms | EMD Serono | November 30, 2013 | Phase 1 |
| NCT00982865 | Completed | Drug: MSC1936369B | Solid Tumors Cancer |
Merck KGaA, Darmstadt, Germany | December 31, 2007 | Phase 1 |
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