fasiglifam   Click here for help

GtoPdb Ligand ID: 6484

Synonyms: TAK 875 | TAK-875 | TAK875
PDB Ligand
Compound class: Synthetic organic
Comment: Fasiglifam is a positive allosteric modulator/partial agonist of the free fatty acid receptor 1 (FFA1, a.k.a. GPR40) [6]. In the presence of endogenous free fatty acids (FFAs) fasiglifam enhances insulin secretion, by binding to an allosteric site distinct from the orthosteric FFA binding site. On its own, it elicits a low level of insulin secretion. These findings indicate that fasiglifam acts cooperatively with FFAs to promote insulin secretion.
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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 4
Hydrogen bond donors 1
Rotatable bonds 11
Topological polar surface area 107.51
Molecular weight 524.19
XLogP 5.72
No. Lipinski's rules broken 2
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 OC(=O)CC1COc2c1ccc(c2)OCc1cccc(c1)c1c(C)cc(cc1C)OCCCS(=O)(=O)C
Isomeric SMILES OC(=O)C[C@@H]1COc2c1ccc(c2)OCc1cccc(c1)c1c(C)cc(cc1C)OCCCS(=O)(=O)C
InChI InChI=1S/C29H32O7S/c1-19-12-25(34-10-5-11-37(3,32)33)13-20(2)29(19)22-7-4-6-21(14-22)17-35-24-8-9-26-23(15-28(30)31)18-36-27(26)16-24/h4,6-9,12-14,16,23H,5,10-11,15,17-18H2,1-3H3,(H,30,31)/t23-/m1/s1
InChI Key BZCALJIHZVNMGJ-HSZRJFAPSA-N
No information available.
Summary of Clinical Use Click here for help
Fasiglifam has been in clinical trial as an antidiabetic drug. However, the News in Brief section of Nature Reviews Drug Discovery (Vol 13, p91 (2014), doi:10.1038/nrd4246) reports termination of a Phase 3 trial of fasiglifam due to unacceptable levels of liver toxicity. Click here to view the Clinicaltrials.gov record for this trial.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Fasiglifam is a GPR40 agonist. GPR40 is a candidate anti-diabetes drug target as it has been shown that agonists of this GPCR modulate insulin secretion from pancreatic β cells [1].