RO4987655 (Synonyms: CH4987655) |
Catalog No.GC12141
One-Click Copy Product Info
|
MEK inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 874101-00-5
Sample solution is provided at 25 µL, 10mM.
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RO4987655 is a highly selective and small molecule inhibitor of MEK with IC50 value of 5nM [1].
RO4987655 is developed with a unique 3-oxo-[1,2]oxazinan-2-ylmethyl group at the 5-position.It is highly selective against MEK over other 400 kinases. Meanwhile, RO4987655 is a non- competitive inhibitor of MEK. It shows higher affinity for MEK both in the absence and the presence of ATP. RO4987655 has a strong anti-proliferation efficacy in various tumor cells including COLO205, HT29, QG56, MIA and C32 with IC50 values of 0.86nM, 1.7nM, 9.5nM, 3.3nM and 8.4nM, respectively. In addition, RO4987655 is found to have antitumor activity in a wide range of human cancer xenograft models. In the HT-29 human colon cancer xenograft, RO4987655 shows a strong inhibition of pERK formation as well as tumor regression [1, 2].
RO4987655 is now in phase I trials. It shows clinical activity in both patients with BRAF wild-type melanoma and BRAF V600-mutated melanoma. It is also efficacious in patients with KRAS-mutated non-small cell lung cancer but not KRAS-mutated colorectal cancer [2].
References:
[1] Isshiki Y, Kohchi Y, Iikura H, Matsubara Y, Asoh K, Murata T, Kohchi M, Mizuguchi E, Tsujii S, Hattori K, Miura T, Yoshimura Y, Aida S, Miwa M, Saitoh R, Murao N, Okabe H, Belunis C, Janson C, Lukacs C, Schück V, Shimma N. Design and synthesis of novel allosteric MEK inhibitor CH4987655 as an orally available anticancer agent. Bioorg Med Chem Lett. 2011 Mar 15;21(6):1795-801.
[2] Zimmer L, Barlesi F, Martinez-Garcia M, Dieras V, Schellens JH, Spano JP, Middleton MR, Calvo E, Paz-Ares L, Larkin J, Pacey S, Venturi M, Kraeber-Bodere F, Tessier JJ, Eberhardt WE, Paques M, Guarin E, Meresse Naegelen V, Soria JC. Phase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655) in selected advanced cancer patients with RAS-RAF mutations. Clin Cancer Res. 2014 Jun 19. pii: clincanres.0341.2014.
Cell experiment: | The human lung adenocarcinoma cell line NCI-H2122 are maintained in the designated media and indicated concentrations of heat-inactivated fetal bovine serum and L-glutamine. Cells are grown at 37°C in an atmosphere of 5%CO2. Cells are treated with various concentrations of RO4987655 (0.00001, 0.001, 0.1, and 10 μM) for 72 h in 96-well plates and viable cells were quantified with Cell Counting Kit-8[2]. |
Animal experiment: | Mice[2]Female athymic nude mice Balb nu/nu, age 5 to 6 weeks (18 to 22 g) are used. NCI-H2122 cells (4×106/mouse) are inoculated subcutaneously in the right flank of Balb-nu/nu mice. Once tumors are established (100 to 200 mm3), mice are randomized into groups with similar mean tumor volumes at the start of the study. The tumors size is estimated with digital caliper and PET scans performed on days 0, 1, and 3 with 1.0, 2.5, and 5.0 mg/kg RO4987655. Tumor volume and body weight are measured on days 0 (baseline), 1, 2, 3, and 9 of [18F] FDG-PET imaging. Tumor growth inhibition is calculated[2]. |
References: [1]. Lee L, et al. The safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of CH4987655 in healthy volunteers: target suppression using a biomarker. Clin Cancer Res. 2009 Dec 1;15(23):7368-74. | |
| Cas No. | 874101-00-5 | SDF | |
| Synonyms | CH4987655 | ||
| Chemical Name | 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(3-oxooxazinan-2-yl)methyl]benzamide | ||
| Canonical SMILES | C1CC(=O)N(OC1)CC2=C(C(=C(C(=C2)C(=O)NOCCO)NC3=C(C=C(C=C3)I)F)F)F | ||
| Formula | C20H19F3IN3O5 | M.Wt | 565.28 |
| Solubility | ≥ 56.6mg/mL in DMSO, Limited solubility in EtOH | 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 | 1.769 mL | 8.8452 mL | 17.6903 mL |
| 5 mM | 353.8 μL | 1.769 mL | 3.5381 mL |
| 10 mM | 176.9 μL | 884.5 μL | 1.769 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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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 saline, 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.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 34 reference(s) in Google Scholar.)