RO4987655

• CAT Number: I005266
• CAS Number: 874101-00-5
• Molecular Formula: C20H19F3IN3O5
• Molecular Weight: 565.3
• Purity: ≥95%
• Target: MEK1/2
• Solubility: DMSO: ≥ 40 mg/mL
• Storage: Store at +4C
• IC50: 5.2 nM
• InChI: 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)
• InChIKey: FIMYFEGKMOCQKT-UHFFFAOYSA-N
• SMILES: O=C1CCCON1CC2=C(F)C(F)=C(NC3=CC=C(I)C=C3F)C(C(NOCCO)=O)=C2

RO4987655(CH-4987655) is an orally active small molecule, targeting mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1 IC50=5.2 nM), with potential antineoplastic activity.IC50 value: 5.2 nMTarget: MEK1/2MEK 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.

Reference

1:Evaluation of efficacy of a new MEK inhibitor, RO4987655, in human tumor xenografts by [(18)F] FDG-PET imaging combined with proteomic approaches. 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.EJNMMI Res. 2014 Dec;4(1):34. doi: 10.1186/s13550-014-0034-6. Epub 2014 Sep 9. PMID: 26116108 Free PMC Article2:Phase I and pharmacokinetics/pharmacodynamics study of the MEK inhibitor RO4987655 in Japanese patients with advanced solid tumors. 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.Invest New Drugs. 2015 Jun;33(3):641-51. doi: 10.1007/s10637-015-0229-3. Epub 2015 Mar 27. PMID: 25809858 3:Phase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655) in selected patients with advanced cancer with RAS-RAF mutations. 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.Clin Cancer Res. 2014 Aug 15;20(16):4251-61. doi: 10.1158/1078-0432.CCR-14-0341. Epub 2014 Jun 19. PMID: 24947927 Free Article4:Phase I dose-escalation study of the safety, pharmacokinetics, and pharmacodynamics of the MEK inhibitor RO4987655 (CH4987655) in patients with advanced solid tumors. 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.Clin Cancer Res. 2012 Sep 1;18(17):4794-805. Epub 2012 Jul 5. PMID: 22767668 Free Article