alloswitch-1   Click here for help

GtoPdb Ligand ID: 8543

Synonyms: trans-alloswitch-1
PDB Ligand
Compound class: Synthetic organic
Comment: Alloswitch-1 is the first reported photo-switchable negative allosteric modulator (NAM) for an endogenous G protein-coupled receptor [2], in this case a NAM of the mGlu5 metabotropic glutamate receptor. Violet light isomerizes the trans molecule to the cis molecule and green light reverses this isomerization [2]. In dark conditions trans-alloswitch-1 antagonizes IP production by quisqualate (orthosteric agonist)-activated mGlu5 receptors. Exposure to violet light reduces this level of antagonism, indicating that the cis-isomer is less active as a NAM than the trans-isomer [2].
The development of photo-switchable compounds is being pursued by pharmaceutical companies as a method to improve pharmacological selectivity by allowing precise spatio-temporal regulation of drug action [1].
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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 1
Rotatable bonds 6
Topological polar surface area 75.94
Molecular weight 366.09
XLogP 5.12
No. Lipinski's rules broken 1
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 COc1cc(N=Nc2ccccn2)ccc1NC(=O)c1ccccc1Cl
Isomeric SMILES COc1cc(/N=N/c2ccccn2)ccc1NC(=O)c1ccccc1Cl
InChI InChI=1S/C19H15ClN4O2/c1-26-17-12-13(23-24-18-8-4-5-11-21-18)9-10-16(17)22-19(25)14-6-2-3-7-15(14)20/h2-12H,1H3,(H,22,25)/b24-23+
InChI Key JJRNGNCTPCWXGM-WCWDXBQESA-N
Bioactivity Comments
The IC50 for antagonism of quisqualate-induced IP accumulation in dark conditions (trans-alloswitch-1) is 8.6nM, compared to 16nM under violet light exposure (cis-alloswitch-1) [2].
Selectivity at GPCRs
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
mGlu5 receptor Primary target of this compound Rn Allosteric modulator Negative 8.1 pIC50 - 2
⤷ pIC50 8.1 (IC50 8.6x10-9 M) [2]
Description: Inhibition of agonist-induced IP accumulation.