BIA 10-2474   Click here for help

GtoPdb Ligand ID: 9001

Synonyms: BIA-10-2474 | BIA-102474 | compound 8 l [PubMed: 30113139] | example 362 [WO2010074588] [3]
Compound class: Synthetic organic
Comment: BIA 10-2474 was believed to be reversible inhibitor of fatty acid amide hydrolase (FAAH). It was the cause of a disastrous clinical trial in France which left one participant dead and several others with serious neurological adverse events. The compound is claimed in patent WO2010074588 [3]. The structure of BIA 10-2474 was disclosed in a clinical trial protocol with EudraCT No: 2015-001799-24. Pharmacological inhibition of FAAH was being investigated in the search for novel analgesic drugs [4-6]. More information surrounding this compound and its unfortunate clinical trial outcome is available in two blogposts by our curator Christopher Southan (The unfortunate case of BIA-10-2474 and Molecular details related to BIA 10-2474).

Subsequent analysis of BIA 10-2474's pharmacology is reported by van Esbroeck et al. (2017) [7]. This anaylsis suggests that BIA 10-2474's interaction with FAAH is in fact irreversible. Using activity-based protein profiling (ABPP), this same study reveals that BIA 10-2474 (and its metabolite BIA 10-2639) engages numerous human off-targets including FAAH2 and several lipid serine hydrolases, such as ABHD6, ABHD11, LIPE, and PNPLA6, and xenobiotic drug-metabolizing enzymes CES1, CES2, and CES3, with greater inhibition of ABHD6 and CES2 compared to PNPLA6. The authors postulate that BIA 10-2474 may act to dramatically alter brain lipid metabolism and that this action may have contributed to the compound's neurotoxicity. In the same assays, this action was not replicated by the clinically tested FAAH inhibitor PF-04457845.

Update: August 2018. BIAL have finally published a primary paper describing their internal characterisation of BIA-10-2474 along with the SAR of that series but only with %inhibition rather than IC50 values [2].
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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
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 3
Hydrogen bond donors 0
Rotatable bonds 4
Topological polar surface area 65.07
Molecular weight 300.16
XLogP 2.52
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 [O-][n+]1cccc(c1)c1ncn(c1)C(=O)N(C1CCCCC1)C
Isomeric SMILES [O-][n+]1cccc(c1)c1ncn(c1)C(=O)N(C1CCCCC1)C
InChI InChI=1S/C16H20N4O2/c1-18(14-7-3-2-4-8-14)16(21)19-11-15(17-12-19)13-6-5-9-20(22)10-13/h5-6,9-12,14H,2-4,7-8H2,1H3
InChI Key DOWVMJFBDGWVML-UHFFFAOYSA-N
Classification Click here for help
Compound class Synthetic organic
IUPAC Name Click here for help
N-cyclohexyl-N-methyl-4-(1-oxidopyridin-1-ium-3-yl)imidazole-1-carboxamide
Synonyms Click here for help
BIA-10-2474 | BIA-102474 | compound 8 l [PubMed: 30113139] | example 362 [WO2010074588] [3]
Database Links Click here for help
GtoPdb PubChem SID 310264779
PubChem CID 46831476
Search Google for chemical match using the InChIKey DOWVMJFBDGWVML-UHFFFAOYSA-N
Search Google for chemicals with the same backbone DOWVMJFBDGWVML
UniChem Compound Search for chemical match using the InChIKey DOWVMJFBDGWVML-UHFFFAOYSA-N
UniChem Connectivity Search for chemical match using the InChIKey DOWVMJFBDGWVML-UHFFFAOYSA-N
Wikipedia BIA 10-2474