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Refametinib

Cat. No. M3633
Refametinib Structure
Synonym:

BAY 86-9766, RDEA119

Size Price Availability Quantity
5mg USD 85 In stock
10mg USD 125 In stock
50mg USD 320 In stock
100mg USD 540 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

Refametinib (BAY 86-9766, RDEA119) is a potent, highly selective and ATP non-competitive inhibitor of MEK1 and MEK2 with IC50 of 19 nM and 47 nM, respectively. Refametinib potently inhibited MEK activity as measured by phosphorylation of ERK1/2 across several human cancer cell lines of different tissue origins and BRAF mutational status with EC50 values ranging from 2.5 to 15.8 nM. RDEA119 inhibits anchorage-dependent growth of human cancer cell lines harboring the gain-of-function V600E BRAF mutant with GI50 values ranging from 67 to 89 nM. Refametinib (BAY 86-9766) exhibited potent antiproliferative activity in HCC cell lines with half-maximal inhibitory concentration values ranging from 33 to 762 nM. BAY 86-9766 was strongly synergistic with sorafenib in suppressing tumor cell proliferation and inhibiting phosphorylation of the extracellular signal-regulated kinase (ERK). Refametinib (BAY 869766, RDEA119) exhibits complete suppression of ERK phosphorylation at fully efficacious doses in mice. Refametinib (BAY 869766, RDEA119) shows a tissue selectivity that reduces its potential for central nervous system-related side effects.

Protocol
Cell Experiment
Cell lines A375, SK-MEI-28, Colo205, HT-29 and BxPC3 cells
Preparation method For anchorage-dependent growth inhibition experiments, plating cells in white 384-well plates at 1,000/20 μL/well or white 96-well microplates at 4,000/100 μL/well. After 24-h incubation at 37 °C, 5% CO2, and 100% humidity,incubating RDEA119 for 48 hours at 37 °C and assayed using CellTiter-Glo. For the 96-well anchorage-independent growth assay, filling wells of an “ultralow binding” plate (Corning) are with 60 μL of a 0.15% agarose solution in complete RPMI 1640. Then, adding 60 μL of complete RPMI 1640 which contains 9,000 cells in 0.15% agarose per well. 24 hourlater , adding 60 μL of a 3 × drug solution in agarose-free complete RPMI 1640 . 7 d later , 36 μL of 6 × 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)- 2H-tetrazolium, adding inner salt reagent per well. After 2 hours at 37 °C, determining absorbance at 490 nm on the M5 plate reader.
Concentrations 10-1000 nM
Incubation time 48 hours
Animal Experiment
Animal models Female athymic nude mice are injected s.c. with A375, HT-29 and A431 tumor; male athymic nude mice with Colo205 tumor
Formulation RDEA119 is dissolved in saline.
Dosages 25 or 50 mg/kg
Administration Orally once daily for 14 days
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 572.34
Formula C19H20F3IN2O5S
CAS Number 923032-37-5
Purity >99%
Solubility DMSO
Storage at -20°C
References

Allosteric MEK1/2 inhibitor refametinib (BAY 86-9766) in combination with sorafenib exhibits antitumor activity in preclinical murine and rat models of hepatocellular carcinoma.
Schmieder R, et al. Neoplasia. 2013 Oct;15(10):1161-71. PMID: 24204195.

BRAF mutation-selective inhibition of thyroid cancer cells by the novel MEK inhibitor RDEA119 and genetic-potentiated synergism with the mTOR inhibitor temsirolimus.
Liu D, et al. Int J Cancer. 2010 Dec 15;127(12):2965-73. PMID: 21351275.

RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer.
Iverson C, et al. Cancer Res. 2009 Sep 1;69(17):6839-47. PMID: 19706763.

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Keywords: Refametinib, BAY 86-9766, RDEA119 supplier, MEK, inhibitors

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