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MedKoo Cat#: 202462 | Name: RO4987655
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

RO4987655, also known as CH4987655, is an orally active small molecule, targeting mitogen-activated protein kinase kinase 1 (MAP2K1 or MEK1), with potential antineoplastic activity. MEK inhibitor RO4987655 binds to and inhibits MEK, which may result in the inhibition of MEK-dependent cell signaling and the inhibition of tumor cell proliferation. MEK, a dual specificity threonine/tyrosine kinase, is a key component of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth; constitutive activation of this pathway has been implicated in many cancers.

Chemical Structure

RO4987655
RO4987655
CAS#874101-00-5

Theoretical Analysis

MedKoo Cat#: 202462

Name: RO4987655

CAS#: 874101-00-5

Chemical Formula: C20H19F3IN3O5

Exact Mass: 565.0322

Molecular Weight: 565.28

Elemental Analysis: C, 42.49; H, 3.39; F, 10.08; I, 22.45; N, 7.43; O, 14.15

Price and Availability

Size Price Availability Quantity
10mg USD 650.00 2 Weeks
200mg USD 2,650.00 2 Weeks
500mg USD 3,850.00 2 Weeks
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Related CAS #
No Data
Synonym
RO4987655; RO-4987655; RO 4987655; CH4987655; CH-4987655; CH 4987655.
IUPAC/Chemical Name
3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)-N-(2-hydroxyethoxy)-5-((3-oxo-1,2-oxazinan-2-yl)methyl)benzamide
InChi Key
FIMYFEGKMOCQKT-UHFFFAOYSA-N
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)
SMILES Code
O=C(NOCCO)C1=CC(CN2OCCCC2=O)=C(F)C(F)=C1NC3=CC=C(I)C=C3F
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not soluble in water.
Shelf Life
>5 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
             
Product Data
Product Data
Instruction
View handling instruction
Biological target:
RO4987655 is a MEK inhibitor (IC50 = 5 nM). It inhibits the proliferation of COLO 205, HT-29, QG56, MIA PaCa-2, and C32 cells with IC50 values of 0.86, 1.7, 9.5, 3.3, and 8.4 nM, respectively. RO4987655 reduces tumor growth in a variety of mouse xenograft models and inhibits the phosphorylation of ERK in tumor tissue in an HT-29 mouse xenograft model. It acts synergistically with the everolimus to reduce tumor volume in an HCT116 mouse xenograft model.
In vitro activity:
To be determined
In vivo activity:
In mouse models of type 2 diabetes, RO4987655 and RO5126766 decreased blood glucose and improved glucose tolerance. There was an increased glucose infusion rate in db/db mice treated with these compounds. This study showed that blood glucose levels are reduced by suppression of MEK1 expression in the liver of db/db mice. Reference: J Diabetes Res. 2016;2016:8264830. https://pubmed.ncbi.nlm.nih.gov/26839898/
Solvent mg/mL mM
Solubility
DMF 15.0 26.54
DMSO 10.0 17.69
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 565.28 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Ueyama A, Ban N, Fukazawa M, Hirayama T, Takeda M, Yata T, Muramatsu H, Hoshino M, Yamamoto M, Matsuo M, Kawashima Y, Iwase T, Kitazawa T, Kushima Y, Yamada Y, Kawabe Y. Inhibition of MEK1 Signaling Pathway in the Liver Ameliorates Insulin Resistance. J Diabetes Res. 2016;2016:8264830. doi: 10.1155/2016/8264830. Epub 2015 Dec 28. PMID: 26839898; PMCID: PMC4709921. 2. Tegnebratt T, Ruge E, Bader S, Ishii N, Aida S, Yoshimura Y, Ooi CH, Lu L, Mitsios N, Meresse V, Mulder J, Pawlak M, Venturi M, Tessier J, Stone-Elander S. Evaluation of efficacy of a new MEK inhibitor, RO4987655, in human tumor xenografts by [(18)F] FDG-PET imaging combined with proteomic approaches. EJNMMI Res. 2014 Dec;4(1):34. doi: 10.1186/s13550-014-0034-6. Epub 2014 Sep 9. PMID: 26116108; PMCID: PMC4452660.
In vitro protocol:
To be determined
In vivo protocol:
1. Ueyama A, Ban N, Fukazawa M, Hirayama T, Takeda M, Yata T, Muramatsu H, Hoshino M, Yamamoto M, Matsuo M, Kawashima Y, Iwase T, Kitazawa T, Kushima Y, Yamada Y, Kawabe Y. Inhibition of MEK1 Signaling Pathway in the Liver Ameliorates Insulin Resistance. J Diabetes Res. 2016;2016:8264830. doi: 10.1155/2016/8264830. Epub 2015 Dec 28. PMID: 26839898; PMCID: PMC4709921. 2. Tegnebratt T, Ruge E, Bader S, Ishii N, Aida S, Yoshimura Y, Ooi CH, Lu L, Mitsios N, Meresse V, Mulder J, Pawlak M, Venturi M, Tessier J, Stone-Elander S. Evaluation of efficacy of a new MEK inhibitor, RO4987655, in human tumor xenografts by [(18)F] FDG-PET imaging combined with proteomic approaches. EJNMMI Res. 2014 Dec;4(1):34. doi: 10.1186/s13550-014-0034-6. Epub 2014 Sep 9. PMID: 26116108; PMCID: PMC4452660.
1: Fang K, Xu Z, Jiang S, Yan C, Tang D, Huang Y. Integrated profiling uncovers prognostic, immunological, and pharmacogenomic features of ferroptosis in triple-negative breast cancer. Front Immunol. 2022 Nov 25;13:985861. doi: 10.3389/fimmu.2022.985861. PMID: 36505498; PMCID: PMC9732280. 2: Ang JE, Pal A, Asad YJ, Henley AT, Valenti M, Box G, de Haven Brandon A, Revell VL, Skene DJ, Venturi M, Rueger R, Meresse V, Eccles SA, de Bono JS, Kaye SB, Workman P, Banerji U, Raynaud FI. Modulation of Plasma Metabolite Biomarkers of the MAPK Pathway with MEK Inhibitor RO4987655: Pharmacodynamic and Predictive Potential in Metastatic Melanoma. Mol Cancer Ther. 2017 Oct;16(10):2315-2323. doi: 10.1158/1535-7163.MCT-16-0881. Epub 2017 Jun 21. PMID: 28637716; PMCID: PMC6112418. 3: Ueyama A, Ban N, Fukazawa M, Hirayama T, Takeda M, Yata T, Muramatsu H, Hoshino M, Yamamoto M, Matsuo M, Kawashima Y, Iwase T, Kitazawa T, Kushima Y, Yamada Y, Kawabe Y. Inhibition of MEK1 Signaling Pathway in the Liver Ameliorates Insulin Resistance. J Diabetes Res. 2016;2016:8264830. doi: 10.1155/2016/8264830. Epub 2015 Dec 28. PMID: 26839898; PMCID: PMC4709921. 4: Tegnebratt T, Ruge E, Bader S, Ishii N, Aida S, Yoshimura Y, Ooi CH, Lu L, Mitsios N, Meresse V, Mulder J, Pawlak M, Venturi M, Tessier J, Stone-Elander S. Evaluation of efficacy of a new MEK inhibitor, RO4987655, in human tumor xenografts by [(18)F] FDG-PET imaging combined with proteomic approaches. EJNMMI Res. 2014 Dec;4(1):34. doi: 10.1186/s13550-014-0034-6. Epub 2014 Sep 9. PMID: 26116108; PMCID: PMC4452660. 5: Nakamichi S, Nokihara H, Yamamoto N, Yamada Y, Fujiwara Y, Tamura Y, Wakui H, Honda K, Mizugaki H, Kitazono S, Tanabe Y, Asahina H, Yamazaki N, Suzuki S, Matsuoka M, Ogita Y, Tamura T. Phase I and pharmacokinetics/pharmacodynamics study of the MEK inhibitor RO4987655 in Japanese patients with advanced solid tumors. Invest New Drugs. 2015 Jun;33(3):641-51. doi: 10.1007/s10637-015-0229-3. Epub 2015 Mar 27. PMID: 25809858. 6: 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-Bodéré F, Tessier JJ, Eberhardt WE, Paques M, Guarin E, Meresse V, Soria JC. Phase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655) in selected patients with advanced cancer with RAS-RAF mutations. Clin Cancer Res. 2014 Aug 15;20(16):4251-61. doi: 10.1158/1078-0432.CCR-14-0341. Epub 2014 Jun 19. PMID: 24947927. 7: Miller CR, Oliver KE, Farley JH. MEK1/2 inhibitors in the treatment of gynecologic malignancies. Gynecol Oncol. 2014 Apr;133(1):128-37. doi: 10.1016/j.ygyno.2014.01.008. Epub 2014 Jan 14. PMID: 24434059. 8: Akinleye A, Furqan M, Mukhi N, Ravella P, Liu D. MEK and the inhibitors: from bench to bedside. J Hematol Oncol. 2013 Apr 12;6:27. doi: 10.1186/1756-8722-6-27. PMID: 23587417; PMCID: PMC3626705. 9: Kraeber-Bodéré F, Carlier T, Naegelen VM, Shochat E, Lumbroso J, Trampal C, Nagarajah J, Chua S, Hugonnet F, Stokkel M, Gleeson F, Tessier J. Differences in the biologic activity of 2 novel MEK inhibitors revealed by 18F-FDG PET: analysis of imaging data from 2 phase I trials. J Nucl Med. 2012 Dec;53(12):1836-46. doi: 10.2967/jnumed.112.109421. Epub 2012 Nov 9. PMID: 23143089. 10: Leijen S, Middleton MR, Tresca P, Kraeber-Bodéré F, Dieras V, Scheulen ME, Gupta A, Lopez-Valverde V, Xu ZX, Rueger R, Tessier JJ, Shochat E, Blotner S, Naegelen VM, Schellens JH, Eberhardt WE. Phase I dose-escalation study of the safety, pharmacokinetics, and pharmacodynamics of the MEK inhibitor RO4987655 (CH4987655) in patients with advanced solid tumors. Clin Cancer Res. 2012 Sep 1;18(17):4794-805. doi: 10.1158/1078-0432.CCR-12-0868. Epub 2012 Jul 5. PMID: 22767668. 11: Lee L, Niu H, Rueger R, Igawa Y, Deutsch J, Ishii N, Mu S, Sakamoto Y, Busse-Reid R, Gimmi C, Goelzer P, De Schepper S, Yoshimura Y, Barrett J, Ishikawa Y, Weissgerber G, Peck R. 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. doi: 10.1158/1078-0432.CCR-09-1696. Epub 2009 Nov 24. PMID: 19934286.

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