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Formula | C16H14F3IN2O4 |
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Molecular Weight | 482.19 | CAS No. | 391210-10-9 | |
Solubility (25°C)* | In vitro | DMSO | 96 mg/mL (199.09 mM) | |
Ethanol | 96 mg/mL (199.09 mM) | |||
Water | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
Description | Mirdametinib (PD0325901) is a selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM in cell-free assays, roughly 500-fold more potent than CI-1040 on phosphorylation of ERK1 and ERK2. Phase 2. | ||
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In vitro | PD0325901 shows higher permeability than CI-1040, another MEK inhibitor. PD0325901 should be able to achieve higher systemic exposures than CI-1040. [1] PD0325901 is exquisitely specific and highly potent against purified MEK, revealing a Kiapp of 1 nM against activated MEK1 and MEK2. [2] PD0325901 is roughly 500-fold more potent than CI-1040 with respect to its cellular effects on phosphorylation of ERK1 and ERK2, displaying subnanomolar activity. [2] PD0325901 prevents the growth of melanoma cell lines. PD0325901 inhibits the growth of TPC-1 cells and K2 cells with GI50 of 11 nM and 6.3 nM, respectively. [3] PD0325901 significantly prevents the the growth of PTC cells harboring a BRAF mutation at very low concentration (10 nM) and only moderately increases the growth of the PTC cells carrying the RET/PTC1 rearrangement at the same concentration. PD0325901 effectively inhibits the phosphorylation of ERK1/2 in multiple PTC cell lines. [3] | ||
In vivo | The improved potency of PD0325901 relative to CI-1040 is evident. A single oral dose of PD0325901 (25 mg/kg) inhibits phosphorylation of ERK by more than 50% at 24 hours post-dosing. In contrast, CI-1040 at a much higher dose (150 mg/kg) only inhibit pERK levels for roughly 8 hours, returning to control levels by 24 hours after treatment. [2] Therefore, the dose required to produce a 70% incidence of complete tumor responses (C26 model) is 25 mg/kg/day versus 900 mg/kg/day for PD0325901 and CI-1040, respectively. Anticancer activity of PD 0325901 has been demonstrated for a broad spectrum of human tumor xenografts. [2] After 1 week of oral administration of PD0325901 (20–25 mg/kg/day) in mice, no tumor growth is detected in mice inoculated with PTC cells bearing a BRAF mutation. [3] For PTC with the RET/PTC1 rearrangement, the average tumor volume of the orthotopic tumor is decreased by 58% as compared with controls. In conclusion, PTC cells carrying a BRAF mutation are more sensitive to PD0325901 than are PTC cells carrying the RET/PTC1 rearrangement. [3] |
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Data from [Data independently produced by Nature, 2015, 517(7534), 391-5]
Data from [Data independently produced by Oncogene, 2015, 10.1038/onc.2015.97]
Data from [Data independently produced by J Bone Joint Surg Am, 2015, 96(14), e117]
Data from [Data independently produced by J Exp Med, 2014, 211(3), 395-404]
Highly efficient construction of monkey blastoid capsules from aged somatic cells [ Nat Commun, 2025, 16(1):1130] | PubMed: 39875393 |
WNK1-dependent water influx is required for CD4+ T cell activation and T cell-dependent antibody responses [ Nat Commun, 2025, 16(1):1857] | PubMed: 39984435 |
Dual-nuclease single-cell lineage tracing by Cas9 and Cas12a [ Cell Rep, 2025, 44(1):115105] | PubMed: 39721023 |
NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing [ Commun Biol, 2025, 8(1):125] | PubMed: 39865169 |
A developmental atlas of mouse vestibular-like inner ear organoids [ iScience, 2025, 28(2):111817] | PubMed: 39967872 |
Expression of the glucose transporter 1 is associated with increased glucose uptake by granulosa cells during ovulation in mice [ Theriogenology, 2025, 236:13-20] | PubMed: 39893797 |
Noncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis [ Sci Adv, 2025, 11(4):eadq2395] | PubMed: 39841821 |
Uncoupling of Akt and mTOR signaling drives resistance to Akt inhibition in PTEN loss prostate cancers [ Sci Adv, 2025, 11(6):eadq3802] | PubMed: 39919177 |
Decaying and expanding Erk gradients process memory of skeletal size during zebrafish fin regeneration [ bioRxiv, 2025, 2025.01.23.634576] | PubMed: 39896678 |
Symbolic recording of signalling and cis-regulatory element activity to DNA [ Nature, 2024, 10.1038/s41586-024-07706-4] | PubMed: 39020177 |
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