PD0325901 Licensed by Pfizer

Catalog No.S1036

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.

Price Stock Quantity  
USD 140 In stock
USD 70 In stock
USD 270 In stock
USD 770 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

PD0325901 Chemical Structure

PD0325901 Chemical Structure
Molecular Weight: 482.19

Validation & Quality Control

Cited by 86 publications:

14 customer reviews :

Quality Control & MSDS

Related Compound Libraries

MEK Inhibitors with Unique Features

Product Information

  • Compare MEK Inhibitors
    Compare MEK Products
  • Research Area
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

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.
Targets MEK [1]
(Cell-free assay)
IC50 0.33 nM
In vitro PF0325901 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]
Features

Protocol(Only for Reference)

Kinase Assay:

[1]

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.

Cell Assay:

[3]

Cell lines PTC cells
Concentrations 0.1 nM- 1 μM
Incubation Time 48 hours
Method

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 GI50 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 GI50, 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.

Animal Study:

[3]

Animal Models Ncr-nu/nu mice bearing PTC cells
Formulation 80 mM citric buffer (pH 7)
Dosages 20-25 mg/kg
Administration Oral gavage

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Barrett SD, et al. Bioorg Med Chem Lett, 2008, 18(24), 6501-6504.

[2] Judith SS, et al. Proc Amer Assoc Cancer Res.2004,45, Abstract #4003

view more

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-30)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02510001 Recruiting Solid Tumour|Colorectal Cancer University of Oxford|Queens University, Belfast|Oxford Un  ...more 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 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

view more

Chemical Information

Download PD0325901 SDF
Molecular Weight (MW) 482.19
Formula

C16H14F3IN2O4

CAS No. 391210-10-9
Storage 3 years -20℃powder
2 years -80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 96 mg/mL (199.09 mM)
Ethanol 40 mg/mL (82.95 mM)
Water <1 mg/mL
In vivo 30% PEG 400+5% Tween 80+ddH2O 10mg/mL
* <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.
Chemical Name (R)-N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzamide

Frequently Asked Questions

  • Question 1
    Whether the inhibitor PD0325901 interacts with other targets other than MEK?

    Answer: 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/

Tech Support

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.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related MEK Products

  • Cobimetinib (GDC-0973, RG7420)

    Cobimetinib (GDC-0973, RG7420) is a potent and highly selective MEK1 inhibitor with IC50 of 4.2 nM. Phase 3.

  • BI-847325

    BI-847325 is an orally bioavailable, and selective dual MEK/Aurora kinase inhibitor with IC50 of 3 nM, 25 nM, 15 nM, 25 nM, and 4 nM for Xenopus laevis Aurora B, human Aurora A and Aurora C, as well as human MEK1 and MEK2, respectively. Phase 1.

  • GDC-0623

    GDC-0623 is a potent and ATP-uncompetitive MEK1 inhibitor with Ki of 0.13 nM. Phase 1.

  • Trametinib (GSK1120212)

    Trametinib (GSK1120212) is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assays, no inhibition of the kinase activities of c-Raf, B-Raf, ERK1/2.

    Features:More potent than PD0325901 or AZD6244.

  • Selumetinib (AZD6244)

    Selumetinib (AZD6244) is a potent, highly selective MEK1 inhibitor with IC50 of 14 nM in cell-free assays, also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. Phase 3.

    Features:First MEK inhibitor being tested in Phase II clinical trials.

  • U0126-EtOH

    U0126-EtOH is a highly selective inhibitor of MEK1/2 with IC50 of 0.07 μM/0.06 μM in cell-free assays, 100-fold higher affinity for ΔN3-S218E/S222D MEK than PD98059.

    Features:A chemically synthesized and highly selective inhibitor of both MEK1 and MEK2.

  • PD98059

    PD98059 is a non-ATP competitive MEK inhibitor with IC50 of 2 μM in a cell-free assay, specifically inhibits MEK-1-mediated activation of MAPK; does not directly inhibit ERK1 or ERK2.

    Features:Does not inhibit c-Raf phosphorylated MEK1.

  • PD184352 (CI-1040)

    PD184352 (CI-1040) is an ATP non-competitive MEK1/2 inhibitor with IC50 of 17 nM in cell-based assays, 100-fold more selective for MEK1/2 than MEK5. Phase 2.

    Features:First MEK inhibitor to begin clinical development.

  • Binimetinib (MEK162, ARRY-162, ARRY-438162)

    Binimetinib (MEK162, ARRY-162, ARRY-438162) is a potent inhibitor of MEK1/2 with IC50 of 12 nM in a cell-free assay. Phase 3.

  • Refametinib (RDEA119, Bay 86-9766)

    Refametinib (RDEA119, Bay 86-9766) is a potent, ATP non-competitive and highly selective inhibitor of MEK1 and MEK2 with IC50 of 19 nM and 47 nM, respectively.

Recently Viewed Items

Tags: buy PD0325901 | PD0325901 supplier | purchase PD0325901 | PD0325901 cost | PD0325901 manufacturer | order PD0325901 | PD0325901 distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us