Source of information: Drugbank (External Link). Last updated on: 3rd July 18
*Trade Name used in the content below may not be the same as the HSA-registered product.
Active Ingredient / Synonyms
Cobimetinib | Cobimetinib |
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. It has been approved in Switzerland and the US, in combination with vemurafenib for the treatment of patients with unresectable or metastatic BRAF V600 mutation-positive melanoma.
For the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. Cobimetinib is used in combination with vemurafenib, a BRAF inhibitor.
Mechanism of Action
MEK inhibitor 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. Cobimetinib and vemurafenib target two different kinases in the RAS/RAF/MEK/ERK pathway.
Cobimetinib is a reversible inhibitor of mitogen-activated protein kinase 1 (MAPK)/extracellular signal regulated kinase 1 (MEK1) and MEK2. Preclinical studies have demonstrated that this agent is effective in inhibiting the growth of tumor cells bearing a BRAF 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 signalling pathway that is frequently activated in human tumors, MEK1 is required for the transmission of growth-promoting signals from numerous receptor tyrosine kinases. Cobimetinib is used in combination with vemurafenib because the clinical benefit of a BRAF inhibitor is limited by intrinsic and acquired resistance. Reactivation of the MAPK pathway is a major contributor to treatment failure in BRAF-mutant melanomas, approximately ~80% of melanoma tumors becomes BRAF-inhibitor resistant due to reactivation of MAPK signalling. BRAF-inhibitor resistant tumor cells are sensitive to MEK inhibition, therefore cobimetinib and vemurafenib will result in dual inhibition of BRAF and its downstream target, MEK.
The bioavailability of cobimetinib is 46%, the AUC and Cmax is unaffected by food.
806L in cancer patients based on a population PK analysis.
Cobimetinib is mainly metabolized via CYP3A oxidation and UGT2B7 glucuronidation with no major metabolites formed.
76% of the dose was recovered in feces with 6.6% as unchanged drug. 17.8% of the dose was recovered in urine with 1.6% as unchanged drug.
Average half life was 44 hours.
The most common adverse effects (>20%) for cobimetinib are diarrhea, photosensitivity reactions, nausea, fever and vomiting.
Although best effort has been made to ensure the information provided is correct and updated, users are advised to visit HSA Official website whenever in doubt. Please see Disclaimers.
We welcome all the content error reporting/feedback. Please contact us @ Text Us!