Cobimetinib

DB05239ApprovedInvestigationalSmall moleculeKinase Inhibitor

Cobimetinib is an antineoplastic agent and selective inhibitor of the mitogen-activated extracellular kinase (MEK) pathway used to treat unresectable or metastatic melanoma. Cobimetinib is an orally active, potent and highly selective small molecule inhibiting mitogen-activated protein kinase kinase 1 (MAP2K1 or MEK1), and central components of the RAS/RAF/MEK/ERK signal transduction pathway.

Mechanism: Cobimetinib is a reversible inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1 (MEK1) and MEK2. MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway, which promotes cellular proliferation. BRAF V600E and K mutations result in constitutive activation of the BRAF pathway which includes MEK1 and MEK2. In mice implanted with tumor cell lines expressing BRAF V600E, cobimetinib inhibited tumor cell growth.
Cobimetinib and vemurafenib target two different kinases in the RAS/RAF/MEK/ERK pathway. Compared to either drug alone, coadministration of cobimetinib and vemurafenib resulted in increased apoptosis in vitro and reduced tumor growth in mouse implantation models of tumor cell lines harboring BRAF V600E mutations. Cobimetinib also prevented vemurafenib-mediated growth enhancement of a wild-type BRAF tumor cell line in an in vivo mouse implantation model.
Curator reviewed · 2 references
Primary indication: Cobimetinib is indicated in combination with vemurafenib for the treatment of unresectable or metastatic melanoma with a BRAF V600E or V600K mutation.Curator reviewed · 7 structured indications
Formula / weight: C₂₁H₂₁F₃IN₃O₂ · 531.318 g/mol (avg)
First approval: Canada, 2016 · United States, 2015 · European Union, 2020
Code names: GDC-0973 · RG-7420 · RO5514041 · XL-518
Brand names: Cotellic