Cobimetinib, sold under the brand name Cotellic, is an anti-cancer medication used to treat melanoma and histiocytic neoplasms. Cobimetinib is a MEK inhibitor. Cobimetinib is marketed by Genentech. Technically, cobimetinib is a selective, reversible allosteric inhibitor of MEK1 and MEK2 that reduces phosphorylation of ERK and downstream MAP kinase pathway signaling, suppressing tumor cell proliferation and survival in MAPK-driven tumors. It is administered orally (tablets) and is most commonly dosed as 60 mg once daily on a 21 days on, 7 days off schedule when used in combination with BRAF inhibitors for BRAF V600 mutant melanoma. The compound displays hepatic metabolism with major contributions from CYP3A, a multi-day apparent terminal half-life that supports once-daily dosing, and exposure that can be affected by strong CYP3A modulators. Safety monitoring focuses on ocular events, cardiac function (QT and left ventricular ejection fraction), skin toxicity, and liver enzymes.
Parent: Cobimetinib
Parent: Cobimetinib
Typical quality control specifications for cobimetinib drug substance and finished product incorporate limits aligned with ICH Q3A and Q3B guidance and common pharmacopeial practice. Example analytical targets used in technical dossiers include assay by validated HPLC method typically not less than 98.0% and not more than 102.0%, water content generally under 1.5% (Karl Fischer), and heavy metals below acceptable pharmacopeial limits (for example total heavy metals often specified at 10 ppm or per regulatory requirement). Related substances are controlled by validated chromatographic methods with individual unspecified impurities often limited to 0.2% or 0.5% depending on qualification status, and the sum of impurities typically controlled to 1.0 to 1.5% as a common specification window; known related compounds such as possible N-oxide or desmethyl-related species are usually assigned individual limits (for example up to 0.5% each) and are qualified according to toxicological risk. Residual solvents are limited per ICH Q3C class limits and microbial and particulate specifications apply for the final dosage form. These parameters are illustrative examples; exact limits come from the approved product specification and regulatory submissions.
Cobimetinib is used to treat certain cancers, most notably unresectable or metastatic melanoma with BRAF V600 mutations in combination with a BRAF inhibitor, and it has documented activity in some histiocytic neoplasms.
Cobimetinib is not classic cytotoxic chemotherapy; it is a targeted small molecule inhibitor that interferes with the MAP kinase signaling pathway in tumor cells.
Yes, Cobimetinib is a selective inhibitor of MEK1 and MEK2.
Cobimetinib binds allosterically to MEK1/2, inhibiting their kinase activity, which prevents phosphorylation of ERK, reduces MAPK pathway signaling, and thereby decreases tumor cell proliferation and survival in tumors dependent on this pathway.
