| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
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Purity: ≥98%
| Targets |
MEK1 (Ki = 1 nM); MEK2 (Ki = 1 nM); MEK1 (IC50 = 0.33 nM)
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|---|---|
| ln Vitro |
PD0325901 shows higher permeability than CI-1040, another MEK inhibitor. In comparison to CI-1040, PD0325901 ought to be able to achieve higher systemic exposures.[1] PD0325901 has a Kiapp of 1 nM against activated MEK1 and MEK2, and it is incredibly specific and potent against purified MEK. [2] When it comes to its cellular effects on the phosphorylation of ERK1 and ERK2, PD0325901 is roughly 500 times more potent than CI-1040 and exhibits subnanomolar activity.[2] PD0325901 stops melanoma cell lines from proliferating. K2 cells and TPC-1 cells both experience growth inhibition from PD0325901, with GI50 values of 11 nM and 6.3 nM, respectively.[3] At a very low concentration (10 nM), PD0325901 significantly suppresses the growth of PTC cells containing a BRAF mutation while only slightly promoting the growth of PTC cells containing a RET/PTC1 rearrangement. In numerous PTC cell lines, PD0325901 efficiently inhibits ERK1/2 phosphorylation.[3]
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| ln Vivo |
Evidently, PD0325901 has greater potency than CI-1040. At 24 hours after administration, a single oral dose of PD0325901 (25 mg/kg) significantly reduces the phosphorylation of ERK. However, pERK levels were only inhibited by CI-1040 at a much higher dose (150 mg/kg), and they were back to normal by 24 hours after treatment.[2] As a result, 25 mg/kg/day, as opposed to 900 mg/kg/day for PD0325901 and CI-1040, is the dose needed to produce a 70% incidence of complete tumor responses (C26 model). A wide range of human tumor xenografts have shown PD 0325901's anticancer activity.[2] Mice injected with PTC cells carrying a BRAF mutation did not develop a tumor after receiving PD0325901 orally for a week (20–25 mg/kg/day).[3] When compared to controls, the average tumor volume of the orthotopic tumor in PTC with the RET/PTC1 rearrangement is decreased by 58%. In conclusion, PTC cells with a BRAF mutation are more sensitive to PD0325901 than PTC cells with a RET/PTC1 rearrangement.[3]
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| Enzyme Assay |
The presence of a glutathione S-transferase fusion protein containing p44MAP kinase (GST-MAPK) and a glutathione S-transferase protein containing p45MEK (GST-MEK) is used to measure the incorporation of 32P into myelin basic protein (MBP). The assay solution had a final concentration of 100 mL and was composed of 20 mM HEPES, pH 7.4, 10 mM MgCl2, 1 mM MnCl2, 1 mM EGTA, 50 mM [gamma-32P]ATP, 10 mg GST-MEK, 0.5 mg GST-MAPK, and 40 mg MBP. Trichloroacetic acid is added to stop reactions after 20 minutes, and the mixture is then filtered through a GF/C filter mat. A 1205 Betaplate is used to measure the amount of 32P retained on the filter mat. To determine dose response curves, PD0325901 is evaluated at a range of doses.
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| Cell Assay |
PTC cells ((1 × 104) are plated in 24-well plates with 1 mL of medium and incubated for 4 days at 37 °C. On day 0, the cells are treated in triplicate with the MEK inhibitor PD0325901 at various concentrations. On day 2 to test GI50 or daily for cell growth curves, 5 mg/mL of MTT dissolved in 0.8% NaCl solution is added to each well (0.2 mL). The cells are incubated with MTT for three hours at 37 °C. The liquid is subsequently aspirated out of the wells and dumped. Using a Synergy HT multidetection microplate reader, stained cells are dissolved in 0.5 mL of DMSO and their absorption at 570 nm is measured. For GI50, cell growth is calculated as 100 × (T − T0)/(C − T0),, where T is the optical density of the wells treated with inhibitors 48 hours after the start of the experiment, T0 is the optical density at time zero, and C is the optical density of the DMSO-only control wells.
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| Animal Protocol |
Mice (10–14 per group) are s.c. cocktail-anesthetized. Inoculated into the thyroid gland are K2 and TPC-1 cells that have been stably infected with a retrovirus expressing luciferase (5×105 cells in 5 μL of RPMI1640 medium), and the mice are then checked every week by Xenogen using Living Image 3.0 software to look for tumor development. PD0325901 is dissolved in 80 mM citric buffer (pH 7) using a sonicator one week after inoculation, and mice are then given daily oral gavage doses of 20 to 25 mg/kg for three weeks (5 days in a row). Only mice with tumor burden or a 20% body weight loss are sacrificed. The formula (V=length×width×depth) is used to calculate tumor volume (V), which is measured using calipers. Mice under control are only given 80 mM citric buffer (pH 7). All in vivo experiments are done at least twice.
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| References |
| Molecular Formula |
C16H14F3IN2O4
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|---|---|
| Molecular Weight |
482.19
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| Exact Mass |
482.00
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| Elemental Analysis |
C, 39.85; H, 2.93; F, 11.82; I, 26.32; N, 5.81; O, 13.27
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| CAS # |
391210-10-9
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| Related CAS # |
Mirdametinib;391210-10-9
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| Appearance |
White to off-white solid powder
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| LogP |
3
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| tPSA |
90.8Ų
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| SMILES |
C1=CC(=C(C=C1I)F)NC2=C(C=CC(=C2F)F)C(=O)NOC[C@@H](CO)O
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| InChi Key |
SUDAHWBOROXANE-SECBINFHSA-N
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| InChi Code |
InChI=1S/C16H14F3IN2O4/c17-11-3-2-10(16(25)22-26-7-9(24)6-23)15(14(11)19)21-13-4-1-8(20)5-12(13)18/h1-5,9,21,23-24H,6-7H2,(H,22,25)/t9-/m1/s1
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| Chemical Name |
N-[(2R)-2,3-dihydroxypropoxy]-3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzamide
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| Synonyms |
Mirdametinib; PD 0325901; PD-0325901; PD0325901; PD-325901; PD 325901; PD325901
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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) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0739 mL | 10.3694 mL | 20.7387 mL | |
| 5 mM | 0.4148 mL | 2.0739 mL | 4.1477 mL | |
| 10 mM | 0.2074 mL | 1.0369 mL | 2.0739 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 |
| NCT05054374 | Active Recruiting |
Drug: Mirdametinib Drug: Fulvestrant |
Breast Cancer Solid Carcinoma |
Memorial Sloan Kettering Cancer Center |
September 14, 2021 | Phase 1 Phase 2 |
| NCT03962543 | Active Recruiting |
Drug: Mirdametinib (PD-0325901) oral capsule or dispersible tablet |
Neurofibromatosis Type 1 (NF1) Plexiform Neurofibroma |
SpringWorks Therapeutics, Inc. | September 29, 2019 | Phase 2 |
| NCT05580770 | Recruiting | Drug: Mirdametinib Drug: BGB-3245 |
Advanced Solid Tumor | SpringWorks Therapeutics, Inc. | February 3, 2023 | Phase 1 Phase 2 |
| NCT04923126 | Recruiting | Drug: Mirdametinib | Low-Grade Glioma Recurrent Low-Grade Glioma |
St. Jude Children's Research Hospital |
February 3, 2023 | Phase 1 Phase 2 |
| NCT03905148 | Recruiting | Drug: Lifirafenib Drug: mirdametinib |
Solid Tumor, Adult | BeiGene | May 1, 2019 | Phase 1 |
PD0325901 inhibits PTC cell growthin vitro.Mol Cancer Ther.2010 Jul;9(7):1968-76.
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PD0325901 suppresses the expression of p-ERK1/2 and induces apoptosis in PTC cells.Mol Cancer Ther.2010 Jul;9(7):1968-76. |
PD0325901 inhibits tumor growth in mice.Mol Cancer Ther.2010 Jul;9(7):1968-76. |
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