Licensed by Pfizer Catalog No.S1036
Molecular Weight(MW): 482.19
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.
Cited by 75 Publications
18 Customer Reviews
Phosphorylation of PPARg in epididymal white adipose tissue in ob/ob mice after treatment with MEK inhibitors. Gene expression in ob/ob epididymal white adipose tissue after treatment with vehicle or either of two MEK inhibitors, PD0325901 or GSK1120212 (n = 7, 7 and 8, respectively). Areas under the curve and gene expression were analysed by analysis of variance.
Nature 2015 517(7534), 391-5. PD0325901 purchased from Selleck.
Immunoblot analysis of Ser9-phosphorylated (that is, inactivated) or total GSK3β, active or total β-catenin Thr202- and Tyr204- phosphorylated or total Erk1/2, and Ser473-phosphorylated or total Akt in control; Bcl2 lymphoma cells treated with ADR for five days, together with pharmacological inhibitors targeting MAPK and PI3K kinase pathways.α -Tubulin was used as a loading control. MAPKi=PD325901.
Nature, 2018, 553(7686):96-100. PD0325901 purchased from Selleck.
c, Examples of CDK2 activity traces aligned to the end of mitosis. Each panel shows different time windows relative to mitosis when mitogens were withdrawn (marked in grey) in d. d, Probability of proliferation (defined as CDK2 activity > 1, 10 h after mitosis) represented as a function of time when inhibitors of MEK (MEKi; 100 nM PD0325901) or of CDK4 (CDK4i; 1 μ M palbociclib) were added or when mitogens were removed, relative to mitosis. Data are mean ± s.e.m. (n = 5 biological replicates).
Nature, 2017. PD0325901 purchased from Selleck.
Rapamycin reduces VCAM expression in vivo. Expression of VCAM-1 mRNA (normalized to CD31) in aortas harvested from mice pretreated with vehicle, rapamycin, or rapamycin + MEK inhibitor (MEK-I; PD0325901) and then injected with TNF (n = 5 per group). Mice were treated as in D. Harvested aortas were analyzed for VCAM-1 expression via immunofluorescence.
J Exp Med 2014 211(3), 395-404. PD0325901 purchased from Selleck.
Plasma MEK inhibitor levels of PD325901 are plotted against % MEK inhibition in brain. One hundred percent pERK levels (0% MEK inhibition) were determined in vehicle-treated rats.Inhibition of pERK activity in brain, lung, and Colo205 tumor in nude xenograft mice treated with 10 mg/kg PD325901.
Cancer Res 2009 PD0325901 purchased from Selleck.
Pharmacological inhibition of MEK (PD0325901) suppresses DR5 expression in cancer cells; this effect is reversible upon stopping of the treatment. The indicated cancer cell lines were exposed to the given concentrations of the inhibitors as indicated for 16 h. TPC-1 cells were treated with 10 uM of the indicated inhibitors for different times as labeled.
Oncogene 2015 10.1038/onc.2015.97. PD0325901 purchased from Selleck.
(B)Effect of MAPK pathway inhibition on FGF9 mediated induction of Fgf23 expression. (D) Western blot analysis of FRS2 and ERK1/2 phosphorylation in UMR 106 cells. Cells were treated for 3h (Western blot) or 24h (qPCR analysis) with FGF9 (50ng/ml), EGF (50ng/ml), PD173074 (250nM), PD0325901 (100nM) and RAF265 (500nM) as indicated. Heparin (10g/ml) was added to all treatments with FGF9. Activation of Fgf23 is shown relative to transcript levels in vehicle treated cells (relative expression of 1). Expression values were normalized to Gapdh mRNA copies and are given as average with SEM (n3). Data were compared by 1 way ANOVA; asterisk indicates p<0.05 with respect to vehicle treated cells.
J Bone Miner Res 2011 26, 2486-2497. PD0325901 purchased from Selleck.
Assessment of in vivo toxicity to MEK inhibitor PD0325901. (A) Weight change in grams is shown for each PD0325901 (PD) treatment group in the MDA-MB-453 xenograft model. Weight change is the difference between pre- and post-treatment weight in each group. PD0325901 treatments were carried out at 5, 10, 15 and 20 mg/kg/day for 30 days, and daily gavage of carrier solution was used as control. *P < 0.01 for PD-5/PD-10 vs. control groups and PD-5/PD-10 vs. PD-15/PD-20 groups using Mann-Whitney U test. Error bars: ±2 SEM. (B) Number of days lost due to toxicity is shown for each PD0325901 treatment group in mouse xenograft model explained in Figure 5A. *P < 0.01 for PD-5/PD-10 vs. PD-15/PD-20 groups.
Breast Cancer Res 2011 13, R36. PD0325901 purchased from Selleck.
The therapeutic effect of AR and MEK inhibitors on in vivo angiogenesis. (A) Angiogenesis index for each in vivo treatment group. Angiogenesis was measured as the number of CD-31-positive blood vessels in a cross-section of each xenograft tumor. CTL: control group; FLU: flutamide; and PD: PD0325901. *P < 0.03 for PD0325901 monotherapy vs. control and **P < 0.03 for combination therapy vs. monotherapy groups using Mann-Whitney U test. Error bars: ±2 SEM. (B) Immunohistochemistry (IHC) was used to measure angiogenesis in a control xenograft tumor. Staining was performed using a CD31 rabbit polyclonal antibody. Original magnification, × 40. (C) IHC was used to measure angiogenesis in a PD0325901 monotherapy tumor. Original magnification, × 40. (D) IHC was used to measure angiogenesis in a xenograft tumor treated with combination therapy. Original magnification, × 40.
Breast Cancer Res 2011 13, R36. PD0325901 purchased from Selleck.
Effects of the MEK inhibitor (MEKi) PD0325901 (PD) and rhBMP-2 (BMP) treatment on histology in an NF1 open fracture model. Treatment with 10 mg/kg of PD0325901 on days 22 through 10 (PD alone) slightly improved bone volume and callus size. Delivery of 10 mg of rhBMP-2 in the collagen sponge (BMP alone) resulted in a large increase in bone volume and callus size. Combination treatment with local rhBMP-2 and systemic PD0325901 (PD 1 BMP) resulted in further increases in new bone volume and total callus volume.Picro Sirius Red and Alcian Blue staining to assess fibrous tissue.
J Bone Joint Surg Am 2015 96(14), e117. PD0325901 purchased from Selleck.
Effect of small molecule inhibitors on reprogramming efficiency of myoblast cell derived from 5 different donors. (A) Reprogramming efficiency is shown as number of colonies from 10^5 starting cells on Y-axes. Ctrl, control condition and addition of small molecule inhibitors are marked. (B) AP staining of reprogrammed myoblast cell lines,from 5 different donors, in wells of 12-well plates at day 18. Ctrl, control condition and additions of small molecule inhibitors are marked.
Stem Cells Dev 2013 PD0325901 purchased from Selleck.
Characterization of rES cells. A: image of normal rES cell colonies on feeder layers. B: rES colonies were positive for AP staining. CeE: rES colonies readily expressed pluripotent markers, Sox2 (C), Oct4 (D), and SSEA-1 (E). Blue, DAPI. Scale bars: 100 um.
J Genet Genomics 2012 39, 643e651. PD0325901 purchased from Selleck.
PD0325901 inhibited the sorafenib-induced RAS/ERK pathway activation and enhanced the cytotoxic effects of sorafenib in resistant cell lines. (A) HUH-7 hepatoma cells treated with sorafenib (5 μM) for 24 h with or without pretreatment with specific kinase inhibitors (PD0325901, 10 μM). Expressions of p-AKT and cleaved PARP were revealed by Western blotting. (B) SK-HEP-1 hepatoma cells treated with sorafenib (5 μM) for 24 h with or without pretreatment with specific kinase inhibitors (PD0325901, 10 μM). Expressions of p-AKT and cleaved PARP were revealed by Western blotting. (C) HUH-7 hepatoma cells treated with sorafenib (5 μM) with or without the kinase inhibitors for 24 h. Proportions of apoptotic cells were evaluated by annexin V labeling. (D) SK-HEP-1 hepatoma cells treated with sorafenib (5 μM) with or without the kinase inhibitors for 24 h. Proportions of apoptotic cells were evaluated by annexin V labeling. (*P<0.05, HUH- 7, SK-HEP-1 are control groups, R-HUH-7, R-SK-HEP-1 are resistant groups).
J Surg Res, 2016, 206(2):371-379. PD0325901 purchased from Selleck.
Inhibition of anchorage-independent growth of lung tumor cell lines by selected inhibitors. Each selected cell line was treated with the indicated inhibitor at 0.1 μM and 1 μM concentrations for two weeks and cell colony size formation was scored under the Nikon inverted-phase microscope.
Int J Proteomics 2011 2011, Article ID 215496. PD0325901 purchased from Selleck.
Breast cancer cells were pretreated with 100ng/ml EGF for 15 min and then treated with the indicated concentrations of PD0325901 for 24 hours.
2010 Dr Zhang of Tianjin Medical University. PD0325901 purchased from Selleck.
Purity & Quality Control
Choose Selective MEK Inhibitors
|Description||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.|
PD0325901 shows higher permeability than CI-1040, another MEK inhibitor. PD0325901 should be able to achieve higher systemic exposures than CI-1040.  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 GI50 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. 
|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.  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.  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.  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. |
In vitro cascade assay: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.
-  Barrett SD, et al. Bioorg Med Chem Lett, 2008, 18(24), 6501-6504.
-  Judith SS, et al. Proc Amer Assoc Cancer Res.2004,45, Abstract #4003
-  Henderson YC, et al. Mol Cancer Ther, 2010, 9(7), 1968-1976.
-  Paterson A, et al. Blood, 2012, 119(7), 1726-1736.
-  Ricciardi MR, et al. J Mol Med (Berl), 2012, 90(10), 1133-1144.
-  Pratilas CA, et al. Cancer Res, 2008, 68(22), 9375-9383.
-  Legrier ME, et al. Cancer Res, 2007, 67(23), 11300-11308.
-  Barrett SD, et al. Bioorg Med Chem Lett, 2008, 18(24), 6501-6504.
|In vitro||DMSO||96 mg/mL (199.09 mM)|
|Ethanol||40 mg/mL (82.95 mM)|
|In vivo||Add solvents to the product individually and in order:
30% PEG 400+5% Tween 80+ddH2O
For best results, use promptly after mixing.
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Clinical Trial Information
|NCT Number||Recruitment||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT02510001||Recruiting||Solid Tumour|Colorectal Cancer||University of Oxford|Queens University, Belfast|Oxford University Hospitals NHS Trust|Velindre NHS Trust|University Hospital, Antwerp|Hospital Vall dHebron|Hopital St Antoine, Paris|European Georges Pompidou Hospital|Pfizer|University of Turin, Italy|Belfast Health and Social Care Trust|Beaumont Hospital|European Commission|Array BioPharma|Q2 solutions|Covance|QPS Holdings||November 2014||Phase 1|
|NCT02096471||Active, not recruiting||Neurofibromatosis Type 1 and Growing or Symptomatic, Inoperable PN||University of Alabama at Birmingham||June 2014||Phase 2|
|NCT02022982||Recruiting||KRAS Mutant Non-Small Cell Lung Cancer|Solid Tumors||Dana-Farber Cancer Institute||January 2014||Phase 1|Phase 2|
|NCT02039336||Recruiting||Colorectal Cancer||The Netherlands Cancer Institute|Pfizer||January 2014||Phase 1|Phase 2|
|NCT02297802||No longer available||Prior Treatment With PD-0325901 With Ongoing Clinical Response||Sharp HealthCare||June 2013||Phase 1|
|NCT01347866||Terminated||Advanced Cancer||Pfizer||October 2011||Phase 1|
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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Frequently Asked Questions
Whether the inhibitor PD0325901 interacts with other targets other than MEK?
PD0325901 has very high selectivity to MEK. In addition, it can also inhibits VEGF activity according to the reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713590/