| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
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Purity: ≥98%
| Targets |
MEK1 (IC50 = 5.2 nM); MEK2 (IC50 = 5.2 nM)
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| ln Vitro |
RO4987655 potently inhibits mitogen-activated protein kinase signaling pathway activation and tumor cell growth, with an in vitro IC50 of 5.2 nM for inhibition of MEK1/2[1]. With an IC50 value of 0.0065 μM, RO4987655 inhibits the proliferation of NCI-H2122 cells in a dose-dependent manner. At doses ranging from 0.1 to 1.0 μM, RO4987655 suppresses pERK1/2 as early as 2 hours into the treatment period[2].
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| ln Vivo |
In xenograft models, RO4987655 (CH4987655) administered orally as a single agent completely eradicates tumors. With a tmax of under one hour, RO4987655 is rapidly absorbed. From 0.5 to 4 mg, exposures are dose-proportional. With a terminal t1/2 of under 25 hours, the disposition is biphasic. Low intersubject variability is observed; the range for Cmax and area-under-the-curve (AUC) is respectively 9%–23% and 14%–25%. At higher doses, pERK inhibition is more than 80% inhibited and exposure dependent. An inhibitory Emax model (Emax ~100%; IC50 40.6 ng/mL) is used in nonlinear mixed-effect modeling to describe the pharmacokinetic-pharmacodynamic relationship[1]. Randomly assigned study groups are made up of female athymic nude mice. Using a digital caliper and on days 0, 1, and 3 with doses of 1.0, 2.5, and 5.0 mg/kg RO4987655, the tumor size is estimated. Over this period, the vehicle treatment does not stop the NCI-H2122 tumor xenograft from growing. On the other hand, treatment with RO4987655 causes tumor growth inhibition (TGI) of 119% at 1.0 mg/kg, 145% at 2.5 mg/kg, and 150% at 5.0 mg/kg on day 3. PET imaging demonstrates that [18F] FDG uptake in the xenografts decreases 24 hours (day 1) after RO4987655 administration[2].
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| Enzyme Assay |
RO4987655 (also known as CH-4987655) is a novel, orally bioavailable and specific small molecule inhibitor of MEK kinase with an IC50 of 5.2 nM for MEK1/MEK2. Mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1), which may have antineoplastic activity, is the target of this medication. With an in vitro IC50 for MEK1/2 inhibition of 5.2 nmol/L, it effectively prevents the activation of the mitogen-activated protein kinase signaling pathway and the growth of tumor cells.
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| Cell Assay |
The heat-inactivated fetal bovine serum and L-glutamine are maintained at the indicated concentrations in the designated media for the human lung adenocarcinoma cell line NCI-H2122. At 37 degrees Celsius and 5% CO2, cells develop. Viable cells were counted using the Cell Counting Kit-8 after cells were exposed to RO4987655 at different concentrations (0.00001, 0.001, 0.1, and 10 μM) for 72 hours in 96-well plates[2].
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| Animal Protocol |
Mice: Mice that are athymic and naked in females It uses balb nu/nu that are 5 to 6 weeks old (18 to 22 g). Balb-nu/nu mice receive a subcutaneous injection of NCI-H2122 cells ((4×106/mouse). Mice are randomized into groups with comparable mean tumor volumes at the beginning of the study once tumors are established (100 to 200 mm3). On days 0, 1, and 3 with doses of 1.0, 2.5, and 5.0 mg/kg RO4987655, PET scans are used to estimate the tumor size. Days 0 (baseline), 1, 2, 3, and 9 of [18F] FDG-PET imaging are used to measure tumor volume and body weight. Calculations are made to determine tumor growth inhibition[2].
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| References |
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| Molecular Formula |
C20H19F3IN3O5
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| Molecular Weight |
565.28
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| Exact Mass |
565.0322
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| Elemental Analysis |
C, 42.49; H, 3.39; F, 10.08; I, 22.45; N, 7.43; O, 14.15
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| CAS # |
874101-00-5
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
C1CC(=O)N(OC1)CC2=CC(=C(C(=C2F)F)NC3=C(C=C(C=C3)I)F)C(=O)NOCCO
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| InChi Key |
FIMYFEGKMOCQKT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H19F3IN3O5/c21-14-9-12(24)3-4-15(14)25-19-13(20(30)26-31-7-5-28)8-11(17(22)18(19)23)10-27-16(29)2-1-6-32-27/h3-4,8-9,25,28H,1-2,5-7,10H2,(H,26,30)
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| Chemical Name |
3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(3-oxooxazinan-2-yl)methyl]benzamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.42 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10% DMSO+ 40% PEG300+ 5% Tween-80+ 45% saline: ≥ 2.5 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7690 mL | 8.8452 mL | 17.6903 mL | |
| 5 mM | 0.3538 mL | 1.7690 mL | 3.5381 mL | |
| 10 mM | 0.1769 mL | 0.8845 mL | 1.7690 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00817518 | Completed | Drug: RO4987655 | Neoplasms | Hoffmann-La Roche | January 2009 | Phase 1 |
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