cobimetinib   Click here for help

GtoPdb Ligand ID: 7626

Synonyms: cobimetinib butyrate | cobimetinib fumarate | cometinib | Cotellic® | GDC-0973 | XL-518 | XL518
Approved drug PDB Ligand
cobimetinib is an approved drug (FDA & EMA (2015))
Compound class: Synthetic organic
Comment: Cobimetinib is an allosteric inhibitor of MEK serine/threonine protein kinases, with selectivity for MEK1 and MEK2 [3].
Note that cobimetinib has been erroneously referred to as cometinib and this has propagated in online resources- cometinib is not an official synonym.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 5
Topological polar surface area 64.6
Molecular weight 531.06
XLogP 4.82
No. Lipinski's rules broken 0
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Canonical SMILES Ic1ccc(c(c1)F)Nc1c(ccc(c1F)F)C(=O)N1CC(C1)(O)C1CCCCN1
Isomeric SMILES Ic1ccc(c(c1)F)Nc1c(ccc(c1F)F)C(=O)N1CC(C1)(O)[C@@H]1CCCCN1
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
No information available.
Summary of Clinical Use Click here for help
Cobimetinib is a MEK inhibitor in Phase 3 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 Click here for help
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].