Refametinib (Synonyms: BAY 869766; RDEA119; ) |
| Catalog No.GC16872 |
레파메티닙(BAY 869766; RDEA119)은 각각 19 nM 및 47 nM의 IC50을 갖는 경구 사용 가능한, 강력한 비-ATP-경쟁적, 선택적 알로스테릭 MEK1/MEK2 억제제입니다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 923032-37-5
Sample solution is provided at 25 µL, 10mM.
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Refametinib is a selective and orally available allosteric inhibitor of MEK 1 and MEK 2 with IC50 values of 19nM and 47nM, respectively [1].
Refametinib is a non–ATP-competitive inhibitor of MEK1/2. It inhibits MEK activity in an in vitro assay with IC50 values of 19nM and 47nM for MEK1 and MEK2, respectively. X-ray shows refametinib binds to an allosteric site of MEK. It does not affect ATP binding but precludes binding to the substrate ERK, thus preventing ERK phosphorylation. Refametinib inhibits MEK with EC50 values ranging from 2.5nM to 15.8nM in a variety of human cancer cells including A375, Colo205, HT-29 and MDA-MB-231. In addition, in the cancer cell lines harboring V600E BRAF mutant, refametinib suppresses cell growth with GI50 values ranging from 67nM to 89nM. Furthermore, in the human melanoma A375 tumor xenograft model, treatment of refametinib causes obvious tumor growth delay and regression. Refametinib also shows tumor growth inhibition in the xenograft model of human Colo205 tumor [1].
References:
[1] Iverson C, Larson G, Lai C, et al. RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer. Cancer research, 2009, 69(17): 6839-6847.
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Kinase experiment: |
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]. |
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Cell experiment: |
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]. |
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Animal experiment: |
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]. |
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References: [1]. Iverson C, et al. RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer. Cancer Res. 2009 Sep 1;69(17):6839-47. |
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| Cas No. | 923032-37-5 | SDF | |
| Synonyms | BAY 869766; RDEA119; | ||
| Chemical Name | N-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]-1-[(2S)-2,3-dihydroxypropyl]cyclopropane-1-sulfonamide | ||
| Canonical SMILES | COC1=CC(=C(C(=C1NS(=O)(=O)C2(CC2)CC(CO)O)NC3=C(C=C(C=C3)I)F)F)F | ||
| Formula | C19H20F3IN2O5S | M.Wt | 572.34 |
| Solubility | ≥ 151.8mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7472 mL | 8.7361 mL | 17.4721 mL |
| 5 mM | 0.3494 mL | 1.7472 mL | 3.4944 mL |
| 10 mM | 0.1747 mL | 0.8736 mL | 1.7472 mL |
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- Purity: >99.50%
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