tafamidis   Click here for help

GtoPdb Ligand ID: 8378

Synonyms: FX-1006 | Vyndamax® | Vyndaqel®
Approved drug PDB Ligand
tafamidis is an approved drug (EMA and UK (2011), FDA (2019))
Compound class: Synthetic organic
Comment: Tafamidis binds potently and selectively to transthyretin (TTR), stabilising protein tetramers, thereby inhibiting the formation of amyloid fibrils [2]. The trade name for this drug is Vyndaqel which contains tafamidis meglumine (PubChem CID 24970412). The Vyndamax brand contains tafamidis parent molecule.
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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 1
Rotatable bonds 2
Topological polar surface area 63.33
Molecular weight 306.98
XLogP 4.02
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 Clc1cc(Cl)cc(c1)c1nc2c(o1)cc(cc2)C(=O)O
Isomeric SMILES Clc1cc(Cl)cc(c1)c1nc2c(o1)cc(cc2)C(=O)O
InChI InChI=1S/C14H7Cl2NO3/c15-9-3-8(4-10(16)6-9)13-17-11-2-1-7(14(18)19)5-12(11)20-13/h1-6H,(H,18,19)
InChI Key TXEIIPDJKFWEEC-UHFFFAOYSA-N
Bioactivity Comments
Tafamidis binds within the thyroxine-binding sites of the TTR complex to stabilise the tetrameric structure [2]. It is able to stabilise wild-type and mutated TTR structures [5]. Information from X-ray crystal structures indicates that tafamidis stabilises the interaction between the two identical homodimers which form the tetrameric TTR complex. The dimer-dimer interaction is a relatively weak association and is the first to fail in tetramer dissociation [3].
Selectivity at other protein targets
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
transthyretin Hs Inhibitor Inhibition 8.7 pKd - 2
⤷ pKd 8.7 (Kd 2x10-9 M) [2]
Ligand mentioned in the following text fields
Transthyretin overview