1. MAPK/ERK Pathway
    Autophagy
  2. MEK
    Autophagy

PD0325901 (Synonyms: PD325901)

Cat. No.: HY-10254 Purity: 99.95%
Handling Instructions

PD0325901 is a selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM, roughly 500-fold more potent than CI-1040 on phosphorylation of ERK1 and ERK2.

For research use only. We do not sell to patients.
PD0325901 Chemical Structure

PD0325901 Chemical Structure

CAS No. : 391210-10-9

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 66 In-stock
5 mg USD 60 In-stock
10 mg USD 108 In-stock
25 mg USD 180 In-stock
50 mg USD 228 In-stock
100 mg USD 348 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

    PD0325901 purchased from MCE. Usage Cited in: Clin Cancer Res. 2014 Nov 1;20(21):5483-95.

    Effects of GSK1904529A and AZD6244 as single agents, respectively, on mediators of IGF-1R- and ERK1/ERK2-signaling pathways.(A–B) Effect of GSK1904529A on phosphorylation of IGF-1R (A) and Erk1/Erk2 (B). (C–E) Effect of AZD6244 on phosphorylation of IGF-1R (C), IGF-1R protein expression levels (D), and phosphorylation of Erk1/Erk2 (E). GSK1904529A is observed to inhibit phosphorylation of IGF-1R in a concentration-dependent manner (A), however shows no inhibitory activity against phosphorylation
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    PD0325901 is a selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM, roughly 500-fold more potent than CI-1040 on phosphorylation of ERK1 and ERK2.

    IC50 & Target

    IC50: 0.33 nM (MEK)

    In Vitro

    PF0325901 shows higher permeability, and 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. 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. PD0325901 prevents the growth of melanoma cell lines. PD0325901 inhibits the growth of TPC-1 cells and K2 cells with GC50 of 11 nM and 6.3 nM, respectively. 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[2]

    In Vivo

    PD0325901 (25 mg/kg, p.o.) inhibits phosphorylation of ERK by more than 50% at 24 hours post-dosing. 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. PD0325901 (20-25 mg/kg/day, p.o.) treatment in mice, shows no tumor growth inoculated with PTC cells bearing a BRAF mutation. For PTC with the RET/PTC1 rearrangement, the average tumor volume of the orthotopic tumor is decreased by 58% as compared with controls. PTC cells carrying a BRAF mutation are more sensitive to PD0325901 than are PTC cells carrying the RET/PTC1 rearrangement[2].

    Clinical Trial
    References
    Preparing Stock Solutions
    Concentration Volume Mass 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
    Please refer to the solubility information to select the appropriate solvent.
    Kinase Assay
    [1]

    Incorporation of 32P into myelin basic protein (MBP) is assayed in the presence of a glutathione S-transferase fusion protein containing p44MAP kinase (GST-MAPK) and a glutathione S-transferase protein containing p45MEK (GST-MEK). The assay solution contained 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 in a final volume of 100 mL. Reactions are stopped after 20 minutes by addition of trichloroacetic acid and filtered through a GF/C filter mat. 32P retained on the filter mat is determined using a 1205 Betaplate. PD0325901 is assessed at various dose ranges in order to determine dose response curves. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [2]

    PD0325901 is dissolved in DMSO.

    PTC cells (1×104) are seeded in 24-well plates with 1 mL of medium for 4 days in a 37°C incubator. MEK inhibitor PD0325901 at varying concentrations is added to the cells in triplicate on day 0. MTT dissolved in 0.8% NaCl solution at 5 mg/mL is added to each well (0.2 mL) on day 2 to test GC50 or every day for cell growth curves. The cells are incubated at 37°C for 3 hours with MTT. The liquid is then aspirated from the wells and discarded. Stained cells are dissolved in 0.5 mL of DMSO and their absorption at 570 nm is measured using a Synergy HT multidetection microplate reader. For GC50, cell growth is calculated as 100×(T−T0)/(C−T0), where T is the optical density of the wells treated with inhibitors after a 48-hour period, T0 is the optical density at time zero, and C is the control optical density with DMSO only. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2]

    PD0325901 is dissolved in 80 mM citric buffer.

    Mice (10-14 per group) are anesthetized s.c. with a cocktail (100 μL/10 g body weight of 10 mg/mL keta-mine and 1 mg/mL xylazine). K2 and TPC-1 cells stably infected with a retrovirus expressing luciferase (5×105 cells in 5 μL RPMI1640 medium) are inoculated into the thyroid gland, and the mice are monitored weekly for tumor growth by Xenogen using Living Image 3.0 software. One week after inoculation, PD0325901 is dissolved in 80 mM citric buffer (pH 7) by sonication and given to mice daily by oral gavage (20-25 mg/kg) for 3 weeks (5 consecutive days/week). Mice are sacrificed only due to tumor burden or loss of 20% of body weight. Tumor sizes are measured with calipers and tumor volume (V) is calculated by the formula (V=length×width×depth). Control mice are given 80 mM citric buffer (pH 7) alone. All in vivo experiments are done at least twice. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    482.19

    Formula

    C₁₆H₁₄F₃IN₂O₄

    CAS No.

    391210-10-9

    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

    DMSO: ≥ 56 mg/mL

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

    Purity: 99.95%

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    Inquiry Information

    Product Name:
    PD0325901
    Cat. No.:
    HY-10254
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