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PD-0325901

Cat. No. M1763
PD-0325901 Structure
Synonym:

PD325901

Size Price Availability Quantity
10mg USD 95 In stock
50mg USD 240 In stock
100mg USD 380 In stock
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Quality Control
Biological Activity

The MEK inhibitor PD-0325901 selectively binds to and inhibits MEK, which results in inhibition of ERK phosphorylation and inhibition of tumor cell proliferation. PD-0325901 is a second generation-analogue of CI-1040 with an IC50 of 1 nmol/l that is more potent and soluble than CI-1040 in vivo, with a single oral dose providing > 50% inhibition at 24 h. The anticancer activity of this compound has also been demonstrated in a variety of human tumor xenografts bearing BRAF mutations.

Protocol
Cell Experiment
Cell lines ME1007, ME4405, ME4686,ME8959, ME10538, and ME13923 human melanoma cell lines
Preparation method For IC50 assays, exponentially growing cells were exposed to increasing concentrations of PD0325901 (0.1–1000 nM) for 24, 48, or 72 hours. Cells were then assayed for cell viability (by trypan blue exclusion test) and counted using a Coulter Counter (Kontron Instruments, Milan, Italy). The IC50 value was calculated according to the Chou-Talalay method using the Calcusyn software.
Concentrations 0.1–1000 nM
Incubation time 24, 48 or 72 h
Animal Experiment
Animal models M14 (BRAFV600E) and ME8959 (wtBRAF) cells bearing mice xenograft model
Formulation 0.5% hydroxypropyl methyl-cellulose plus 0.2% Tween 80
Dosages 50 mg/kg per day
Administration oral gavage
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
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.

Chemical Information
Molecular Weight 482.19
Formula C16H14F3IN2O4
CAS Number 391210-10-9
Purity 100.00%
Solubility DMSO ≥96 mg/mL
Storage at -20°C
Customer Product Validations & Biological Datas
Source Oncotarget (2017). PD-325901, Figure 4. (AbMole Bioscience, Hong-Kong, China)
Method Western blot
Cell Lines ATC cell
Concentrations 5 mg/kg
Incubation Time 24 h
Results Interestingly, PD-325901 treated mice presented a 40% tumor burden reduction after 6 weeks of treatment and remained stable for the rest of the experiment. Strikingly, the combination treated animals had a more pronounced response with a 60% tumor burden reduction after 7 weeks (Figure 4A). Interestingly, PD-325901 treated mice showed a clear improvement in histology with some almost normal follicles and smaller PTC areas. GDC-0941 did not induce a beneficial effect at the histological level. Finally, mice treated with the combination, although resulting in smaller sections, seemed to have a similar histological presentation to PD-325901 alone treated animals (Figure 4C).
Rating
Source Oncotarget (2017). PD-325901, Figure 3. (AbMole Bioscience, Hong-Kong, China)
Method Western blot
Cell Lines ATC cell
Concentrations
Incubation Time 24 h
Results ERK1/2 and AKT phosphorylation were assessed first to demonstrate the drug efficiency. ERK1/2 phosphorylation ratio (p-ERK1/2 normalized to total ERK) was strongly decreased in all cell lines when treated with PD-325901 alone or in combination with GDC-0941. Similarly, GDC-0941 induced a strong reduction of AKT phosphorylation ratio (Figure 3).
Rating
Source Oncotarget (2017). PD-325901, Figure 2. (AbMole Bioscience, Hong-Kong, China)
Method apoptosis assay
Cell Lines OCUT-2 cells
Concentrations 100 nM
Incubation Time 24 h
Results Only the OCUT-2 cell line already showed increased apoptosis (double positive annexinV and PI cells) when treated with the combination for 24 h (Figure 2A). However, after 48 h of combination treatment, all three cell lines (Figure 2B and Supplementary Figure 1) had elevated double positive annexinV/PI cells (late apoptosis) and annexinV positive cells (early apoptosis).
Rating
Source Oncotarget (2017). PD-325901, Figure 1. (AbMole Bioscience, Hong-Kong, China)
Method
Cell Lines SW1736 and OCUT-2 cell lines
Concentrations 100 nM, 20 nM, 4 nM, 0.8 nM, 0.16 nM
Incubation Time 72 h
Results We investigated the effect of the drugs on cell cycling. PD-325901 alone or in combination with GDC-0941 induced a G1 cycle arrest in SW1736 and 8505c cell lines. However, in OCUT-2, a significant effect was only observed for the combination (Figure 1C).
Rating
Product Citations
References

Epithelial Tissue Hyperplasia Induced by the RAF Inhibitor PF-04880594 is Attenuated by a Clinically Well-Tolerated Dose of the MEK Inhibitor PD-0325901.
Torti et al. Mol Cancer Ther. 2012 Jul 2. PMID: 22752429.

A novel SND1-BRAF fusion confers resistance to c-Met inhibitor PF-04217903 in GTL16 cells though MAPK activation.
Lee et al. PLoS One. 2012;7(6):e39653. PMID: 22745804.

Combination of a MEK inhibitor at sub-MTD with a PI3K/mTOR inhibitor significantly suppresses growth of lung adenocarcinoma tumors in Kras(G12D-LSL) mice.
Simmons et al. Cancer Chemother Pharmacol. 2012 Aug;70(2):213-20. PMID: 22684718.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: PD-0325901, PD325901 supplier, MEK, inhibitors

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