Name: Refametinib (RDEA119)
Brand: Selleck Chemicals
SKU: S1089
Availability: InStock
Rating: 5 (28 reviews)

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Quality Control

Batch: Purity: 99.91%

99.91

Related Targets	ERK p38 MAPK Raf JNK Ras KRas S6 Kinase MAP4K TAK1 Mixed Lineage Kinase
Other MEK Inhibitors	PD0325901 (Mirdametinib) U0126-EtOH PD 98059 PD184352 (CI-1040) BIX 02189 Pimasertib (AS-703026) TAK-733 AZD8330 BIX 02188 SL-327

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (174.72 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (8.74mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.710mg/ml (1.24mM)	Taking the 1 mL working solution as an example, add 50 μL of 14.2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

+

%

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	572.34	Formula	C₁₉H₂₀F₃IN₂O₅S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	923032-37-5	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	Bay 86-9766			Smiles	COC1=CC(=C(C(=C1NS(=O)(=O)C2(CC2)CC(CO)O)NC3=C(C=C(C=C3)I)F)F)F

Mechanism of Action

Targets/IC₅₀/Ki	MEK1 (Cell-free assay) 19 nM MEK2 (Cell-free assay) 47 nM
In vitro	Refametinib (RDEA119) is selectively bound directly to an allosteric pocket in the MEK1/2 enzymes, and highly efficacious at inhibiting cell proliferation in several tumor cell lines, including A375, SK-MEI-28, Colo205, HT-29 and BxPC3. It 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. Under anchorage-independent conditions, GI50 values for all cell lines tested are similar (40-84 nM). This compound shows a tissue selectivity that reduces its potential for central nervous system–related side effects. It potently inhibits the proliferation of the 4 cell lines that harbored BRAF mutation but has no or modest effects on the other 4 cells that harbored wild-type BRAF (IC50 of 0.034-0.217 μM vs. 1.413-34.120 μM). The inhibitory effect of Refametinib in selected cell lines OCUT1 (BRAF V600E(+), PIK3CA H1047R(+)) and SW1376 (BRAF V600E(+)) is enhanced by combination with the mTOR inhibitor, temsirolimus. It and temsirolimus also show synergistic effects on autophagic death of OCUT1 and KAT18 cells selectively tested.
Kinase Assay	MEK Kinase Assay
Kinase Assay	Kinase inactive murine ERK2 (mERK2) K52A/T183A is affinity purified from Escherichia coli expressed using the pET21a vector. MEK1 kinase activity is determined using mERK2 K52A T183A as the substrate. Recombinant MEK1 enzyme (5 nM) is first activated by 0.02 unit or 1.5 nM of RAF1 in the presence of 25 mM HEPES (pH 7.8), 1 mM MgCl₂, 50 mM NaCl, 0.2 mM EDTA, and 50 μM ATP for 30 minutes at 25 °C. The reactions are initiated by adding 2 μM of mERK2K52A T183A and 2.5 μCi [γ-³³P] ATP in a total volume of 20 μL. The MEK2 kinase activity is determined similarly except that activation by RAF1 is not needed and 11 nM of MEK2 enzyme (active) are used in the assays. Kinase profiling for Refametinib (RDEA119) is performed by Invitrogen using their Select Screen Kinase Profiling Service. The Z'-LYTE biochemical assay is used. This compound is assayed in quadruplicate at 10 μM against 205 kinases.
In vivo	Oral administration of RDEA119 at 50 mg/kg on a once daily × 14 schedule leads to a 68% tumor growth inhibition (TGI) in human melanoma A375 tumor model. This compound at 25 mg/kg on a once daily × 14 schedule results in a 123% TGI in human colon carcinoma Colo205 tumor model (TGI > 100% occurs when the tumor shrinks below its starting volume). A dose of 25 mg/kg once daily × 14 produces 56% and 67% TGI for HT-29 and A431 tumors, respectively.
References	[1] https://pubmed.ncbi.nlm.nih.gov/19706763/ [2] https://pubmed.ncbi.nlm.nih.gov/21351275/

Applications

Methods	Biomarkers	Images	PMID
Growth inhibition assay	IC50		29896883
Western blot	p-BRAF / BRAF / p-MEK / MEK / p-ERK / ERK Cyclin D1 / Cyclin E / p27 p-STAT3 / STAT3		29896883

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01392521	Completed	Neoplasms	Bayer	July 2011	Phase 1
NCT00785226	Completed	Advanced Cancer	Bayer	November 2008	Phase 1\|Phase 2

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Refametinib (RDEA119) MEK inhibitor

Chemical Structure

Molecular Weight: 572.34