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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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: cobimetinib

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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
InChI Key BSMCAPRUBJMWDF-KRWDZBQOSA-N
References
1. Ascierto PA, Kirkwood JM, Grob JJ, Simeone E, Grimaldi AM, Maio M, Palmieri G, Testori A, Marincola FM, Mozzillo N. (2012)
The role of BRAF V600 mutation in melanoma.
J Transl Med, 10: 85. [PMID:22554099]
2. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W et al.. (2002)
Mutations of the BRAF gene in human cancer.
Nature, 417 (6892): 949-54. [PMID:12068308]
3. Rice KD, Aay N, Anand NK, Blazey CM, Bowles OJ, Bussenius J, Costanzo S, Curtis JK, Defina SC, Dubenko L et al.. (2012)
Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization Efforts toward XL518 (GDC-0973).
ACS Med Chem Lett, 3 (5): 416-21. [PMID:24900486]
4. Wan PT, Garnett MJ, Roe SM, Lee S, Niculescu-Duvaz D, Good VM, Jones CM, Marshall CJ, Springer CJ, Barford D et al.. (2004)
Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF.
Cell, 116 (6): 855-67. [PMID:15035987]