Ligand id: 7626

Name: cobimetinib

IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: cobimetinib

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 5
Topological polar surface area 64.6
Molecular weight 531.06
XLogP 4.65
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

No information available.
Summary of Clinical Use
Cobimetinib is a MEK inhibitor in Phase III clinical trial for several types of cancer (see for a listing of current trials). A significant increase in progression-free survival (PFS) has been observed (but not yet publlished, July 2014) in the CoBRIM trial assessing cobimetinib plus the BRAF inhibitor vemurafenib in patients with BRAFV600 mutation-positive unresectable locally advanced or metastatic melanoma. Subsequently, in November 2015, the US FDA approved the cobimetinib/vemurafenib combination therapy to treat metastatic or unresectable BRAFV600E and BRAFV600K melanomas.
Mechanism Of Action and Pharmacodynamic Effects
Cobimetinib selectively inhibits the activity of the MEK serine/threonine protein kinase. MEK is part of a key pathway that promotes cell division and survival, known as the RAS-RAF-MEK-ERK pathway. The BRAF constituent of the pathway frequently carries activating mutations in human cancers, including melanoma [4]. One of the most common cancer-associated mutations is the BRAFV600E mutation [1-2].