Refametinib
Based on 16 publication(s) in Google Scholar
Refametinib (BAY 869766; RDEA119) is an orally available, potent, non-ATP-competitive, selective, allosteric MEK1/MEK2 inhibitor with IC50s of 19 nM and 47 nM, respectively.
For research use only. We do not sell to patients.
- Purity: 99.82%
- CAS No.: 923032-37-5
- Formula: C19H20F3IN2O5S
- Molecular Weight:572.34
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Publications Citing Use of MedChemExpress (MCE) Refametinib
More- Nat Nanotechnol. 2021 Jul;16(7):830-839. [Abstract]
- Cancer Res. 2024 Jun 14;84(12):1963-1977. [Abstract]
- Mol Cell. 2021 Oct 7;81(19):4076-4090.e8. [Abstract]
- Sci Transl Med. 2018 Jul 18;10(450):eaaq1093. [Abstract]
- Cell Death Differ. 2026 Apr 4. [Abstract]
- Neuro Oncol. 2019 Mar 18;21(4):486-497. [Abstract]
- Sci Data. 2024 Sep 19;11(1):1024. [Abstract]
- J Invest Dermatol. 2022 Mar;142(3 Pt A):613-623.e7. [Abstract]
- Biomolecules. 2021 Mar 30;11(4):518. [Abstract]
- Comput Struct Biotechnol J. 2019 Feb 8:17:352-361. [Abstract]
- J Proteome Res. 2022 Apr 1;21(4):953-964. [Abstract]
- Appl Sci. 2023 Mar 29, 13(7), 4340.
- PLoS One. 2023 Mar 10;18(3):e0282166. [Abstract]
- bioRxiv. 2026 May 21:2026.05.19.726303. [Abstract]
- Oncotarget. 2020 Nov 3;11(44):3921-3932. [Abstract]
- ACS Comb Sci. 2019 Dec 9;21(12):805-816. [Abstract]
Customer Validation & Images
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Cell Proliferation/Viability Assay
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WB
All MEK Isoforms
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Biological Activity
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MEK1 19 nM (IC50) |
MEK2 47 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A549 | CC50 |
>100 μM
Compound: 54; RDEA-119
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Cytotoxicity against human A549 cells
Cytotoxicity against human A549 cells
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[PMID: 33539089] |
Refametinib (BAY 869766; RDEA119) selectively binds directly to an allosteric pocket in the MEK1/2 enzymes. Refametinib potently inhibits MEK activity in enzyme inhibition assays in a non-ATP-competitive manner (MEK1 IC50=19 nM, MEK2 IC50=47 nM) determined through incorporation of radioactive phosphate from ATP into ERK as substrate. Refametinib potently inhibits 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. Refametinib 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. In contrast, Refametinib has significantly less growth-inhibitory potency against cell lines with wild-type BRAF (A431 cells) or MDA-MB-231 cells harboring a BRAF mutation G464V that shows minimal (<2-fold increase) enhancement of inherent kinase activity. Under anchorage-independent conditions, GI50 values for all cell lines tested are similar (40-84 nM). MDA-MB-231 and A431 cells are significantly more sensitive to Refametinib under anchorage-independent conditions[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 923032-37-5
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Appearance Solid
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Molecular Weight 572.34
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Formula C19H20F3IN2O5S
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Color Light yellow to brown
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SMILES
O=S(C1(C[C@H](O)CO)CC1)(NC(C(NC(C(F)=C2)=CC=C2I)=C3F)=C(OC)C=C3F)=O
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Synonyms
BAY 869766; RDEA119
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (16)
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Journal Impact Factor
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Most Recent
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Nat Nanotechnol
Therapeutically reprogrammed nutrient signalling enhances nanoparticulate albumin bound drug uptake and efficacy in KRAS-mutant cancer. [Abstract]2021 Jul;16(7):830-839. PMID: 33958764 -
Cancer Res
Oncogenic KRAS induces arginine auxotrophy and confers a therapeutic vulnerability to SLC7A1 inhibition in non-small cell lung cancer. [Abstract]2024 Jun 14;84(12):1963-1977. PMID: 38502865 -
Mol Cell
A proteomic and phosphoproteomic landscape of KRAS mutant cancers identifies combination therapies. [Abstract]2021 Oct 7;81(19):4076-4090.e8. PMID: 34375582 -
Sci Transl Med
PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]2018 Jul 18;10(450):eaaq1093. PMID: 30021885 -
Cell Death Differ
RIPK3 sequentially recruits MLKL and RIPK1 to induce PANoptosis and chemokine production. [Abstract]2026 Apr 4. PMID: 41935203 -
Neuro Oncol
Preclinical assessment of MEK1/2 inhibitors for neurofibromatosis type 2-associated schwannomas reveals differences in efficacy and drug resistance development. [Abstract]2019 Mar 18;21(4):486-497. PMID: 30615146 -
Sci Data
High-throughput drug screening identifies novel therapeutics for Low Grade Serous Ovarian Carcinoma. [Abstract]2024 Sep 19;11(1):1024. PMID: 39300112 -
J Invest Dermatol
Combined Cyclin-Dependent Kinase Inhibition Overcomes MAPK/Extracellular Signal-Regulated Kinase Kinase Inhibitor Resistance in Plexiform Neurofibroma of Neurofibromatosis Type I. [Abstract]2022 Mar;142(3 Pt A):613-623.e7. PMID: 34534577 -
Biomolecules
Allosteric Kinase Inhibitors Reshape MEK1 Kinase Activity Conformations in Cells and In Silico. [Abstract]2021 Mar 30;11(4):518. PMID: 33808483 -
Comput Struct Biotechnol J
Unveiling the Kinomes of Leishmania infantum and L. braziliensis Empowers the Discovery of New Kinase Targets and Antileishmanial Compounds. [Abstract]2019 Feb 8:17:352-361. PMID: 30949306 -
J Proteome Res
An Integrative Proteome-Based Pharmacologic Characterization and Therapeutic Strategy Exploration of SAHA in Solid Malignancies. [Abstract]2022 Apr 1;21(4):953-964. PMID: 35172096 -
Refametinib purchased from MedChemExpress. Usage Cited in: Appl Sci. 2023 Mar 29, 13(7), 4340.
Refametinib (50 nM; 1 h) significantly decreases cell viability in SCC4 Cells.
Refametinib purchased from MedChemExpress. Usage Cited in: Appl Sci. 2023 Mar 29, 13(7), 4340.
Refametinib (50 nM; 1 h) significantly increases the expression of PARP and Caspase-3 in SCC4 Cells.
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PLoS One
Investigation of the anti-tumor mechanism of tirabrutinib, a highly selective Bruton's tyrosine kinase inhibitor, by phosphoproteomics and transcriptomics. [Abstract]2023 Mar 10;18(3):e0282166. PMID: 36897912 -
bioRxiv
Stage-Specific Regulation of DNA Damage Repair by the Circadian Regulator, CRY1, in Prostate Cancer. [Abstract]2026 May 21:2026.05.19.726303. PMID: 42239372 -
Oncotarget
2020 Nov 3;11(44):3921-3932. PMID: 33216841 -
ACS Comb Sci
Benzimidazolyl-pyrazolo[3,4- b]pyridinones, Selective Inhibitors of MOLT-4 Leukemia Cell Growth and Sea Urchin Embryo Spiculogenesis: Target Quest. [Abstract]2019 Dec 9;21(12):805-816. PMID: 31689077
Solvent & Solubility
DMSO : ≥ 31 mg/mL (54.16 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (4.37 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
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 min at 25°C. The reactions are initiated by adding 2 μM of mERK2 K52A 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 is performed. The Z'-LYTE biochemical assay is used. Refametinib is assayed in quadruplicate at 10 μM against 205 kinases[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
For anchorage-dependent growth inhibition experiments, A375, SK-Mel-28, A431, Colo205, HT-29, MDA-MB-231, and BxPC3 cell lines are plated 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, Refametinib is incubated for 48 h at 37°C and assayed using CellTiter-Glo. For the 96-well anchorage-independent growth assay, wells of an “ultralow binding” plate are filled with 60 μL of a 0.15% agarose solution in complete RPMI 1640. Then, 60 μL of complete RPMI 1640 containing 9,000 cells in 0.15% agarose are added per well. After 24 h, 60 μL of a 3× drug solution in agarose-free complete RPMI 1640 are added. After 7 d, 36 μL of 6× MTS reagent are added per well. After 2 h at 37°C, absorbance at 490 nm is determined on the M5 plate reader. Nonlinear curve fitting is performed using GraphPad Prism 4[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Mice[1]
Female athymic nude mice are used for all the efficacy studies except for the Colo205 study 2, which used male mice. Mice are injected s.c. in the flank with 1×106 tumor cells (Colo205 and A431) or ~1 mm3 tumor fragments (A375 and HT-29). Tumor volumes are monitored by caliper measurements. For efficacy analysis, treatment is initiated when tumors are 80 to 185 mm3. Refametinib (25 and 50 mg/kg/d) is administered by oral gavage once daily or twice daily for 14 d or once every 2 d for 14 doses[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (283 KB)
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SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Korean - KR (396 KB)
- Portuguese - PT (396 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.7472 mL | 8.7361 mL | 17.4721 mL | 43.6803 mL |
| 5 mM | 0.3494 mL | 1.7472 mL | 3.4944 mL | 8.7361 mL | |
| 10 mM | 0.1747 mL | 0.8736 mL | 1.7472 mL | 4.3680 mL | |
| 15 mM | 0.1165 mL | 0.5824 mL | 1.1648 mL | 2.9120 mL | |
| 20 mM | 0.0874 mL | 0.4368 mL | 0.8736 mL | 2.1840 mL | |
| 25 mM | 0.0699 mL | 0.3494 mL | 0.6989 mL | 1.7472 mL | |
| 30 mM | 0.0582 mL | 0.2912 mL | 0.5824 mL | 1.4560 mL | |
| 40 mM | 0.0437 mL | 0.2184 mL | 0.4368 mL | 1.0920 mL | |
| 50 mM | 0.0349 mL | 0.1747 mL | 0.3494 mL | 0.8736 mL |
Refametinib Related Classifications
HY-14691 Related Classifications
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