Cobimetinib

• CAT Number: I005550
• CAS Number: 934660-93-2
• Molecular Formula: C₂₁H₂₁F₃IN₃O₂
• Molecular Weight: 531.31
• Purity: ≥95%
• Synonyms: GDC-0973; XL518；Cotellic.
• Target: MEK1/2
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IUPAC Name: [3,4-difluoro-2-(2-fluoro-4-iodoanilino)phenyl]-[3-hydroxy-3-[(2S)-piperidin-2-yl]azetidin-1-yl]methanone
• InChI: InChI=1S/C21H21F3IN3O2/c22-14-6-5-13(19(18(14)24)27-16-7-4-12(25)9-15(16)23)20(29)28-10-21(30,11-28)17-3-1-2-8-26-17/h4-7,9,17,26-27,30H,1-3,8,10-11H2/t17-/m0/s1
• InChIKey: BSMCAPRUBJMWDF-KRWDZBQOSA-N
• SMILES: C1CCN[C@@H](C1)C2(CN(C2)C(=O)C3=C(C(=C(C=C3)F)F)NC4=C(C=C(C=C4)I)F)O

Cobimetinib(Cat No.:I005550) is an orally bioavailable small-molecule inhibitor of mitogen-activated protein kinase kinase 1 (MAP2K1 or MEK1), with potential antineoplastic activity. Cobimetinib specifically binds to and inhibits the catalytic activity of MEK1, resulting in inhibition of extracellular signal-related kinase 2 (ERK2) phosphorylation and activation and decreased tumor cell proliferation. Preclinical studies have demonstrated that this agent is effective in inhibiting the growth of tumor cells bearing a B-RAF mutation, which has been found to be associated with many tumor types. A threonine-tyrosine kinase and a key component of the RAS/RAF/MEK/ERK signaling pathway that is frequently activated in human tumors, MEK1 is required for the transmission of growth-promoting signals from numerous receptor tyrosine kinases.

Overview of Clinical Research

Originator: Exelixis
Developer: Bristol-Myers Squibb; Exelixis; Genentech; InxMed; M. D. Anderson Cancer Center; Massachusetts General Hospital; Memorial Sloan-Kettering Cancer Center; Roche; University Hospital Tubingen
Class: Antineoplastics; Azetidines; Fluorobenzenes; Iodobenzenes; Small molecules
Mechanism of Action: Mitogen-activated protein kinase kinase inhibitors
Orphan Drug Status: Yes – Malignant melanoma
New Molecular Entity:Yes

Reference

[1]. Hoeflich KP, et al. Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC-0941 triggers robust apoptosis and tumor growth inhibition. Cancer Res. 2012 Jan 1;72(1):210-9. 

[2]. Choo EF, et al. PK-PD modeling of combination efficacy effect from administration of the MEK inhibitor GDC-0973 and PI3K inhibitor GDC-0941 in A2058 xenografts. Cancer Chemother Pharmacol. 2013 Jan;71(1):133-43.

[3]. Wong H, et al. Bridging the gap between preclinical and clinical studies using pharmacokinetic-pharmacodynamic modeling: an analysis of GDC-0973, a MEK inhibitor. Clin Cancer Res. 2012 Jun 1;18(11):3090-9.