bitopertin   Click here for help

GtoPdb Ligand ID: 7546

Synonyms: paliflutine | RG1678 | RO-4917838
Compound class: Synthetic organic
Comment: Bitopertin is a non-competitive glycine transporter 1 (GlyT1) inhibitor (functionally a glycine reuptake inhibitor) that was developed by Roche as a potential anti-schizophrenia drug. Its chemical structure is represented in ChEMBL by the R-isomer, CHEMBL1169880.
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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 6
Hydrogen bond donors 0
Rotatable bonds 8
Topological polar surface area 88.19
Molecular weight 543.11
XLogP 5.38
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 Fc1cc(cnc1N1CCN(CC1)C(=O)c1cc(ccc1OC(C(F)(F)F)C)S(=O)(=O)C)C(F)(F)F
Isomeric SMILES Fc1cc(cnc1N1CCN(CC1)C(=O)c1cc(ccc1O[C@H](C(F)(F)F)C)S(=O)(=O)C)C(F)(F)F
InChI InChI=1S/C21H20F7N3O4S/c1-12(20(23,24)25)35-17-4-3-14(36(2,33)34)10-15(17)19(32)31-7-5-30(6-8-31)18-16(22)9-13(11-29-18)21(26,27)28/h3-4,9-12H,5-8H2,1-2H3/t12-/m0/s1
InChI Key YUUGYIUSCYNSQR-LBPRGKRZSA-N
No information available.
Summary of Clinical Use Click here for help
Bitopertin was investigated as an anti-schzophrenia drug [4,6]. Treatment with bitopertin produced promising results for treatment of negative symptoms in schizophrenia in phase 2, but this efficacy was not confirmed in larger phase 3 trials. As a result Roche terminated development in schizphrenia following the disappointing Phase 3 trial results [2-3]. Phase 2 evaluation of bitopertin plus SSRI therapy in patients with obsessive-compulsive disorder has been completed (NCT01674361). Click here to link to to ClinicalTrials.gov's list of registered bitopertin trials.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Bitopertin is a glycine transporter type 1 (GlyT1, SLC6A9) inhibitor [5]. Inhibition of this transporter increases levels of the excitatory neurotransmitter, glycine, by inhibiting its reuptake from the synaptic cleft. Glycine, alongside glutamate, is required as a co-agonist at N-methyl-D-aspartate (NMDA) receptors. Dysfunction of NMDA receptors is believed to play a role in the pathogenesis of schizophrenia. Bitopertin-induced activation of NMDA receptors improves the symptoms of schizophrenia.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01674361 A Study of Bitopertin (RO4917838) in Combination With Selective Serotonin Reuptake Inhibitors (SSRIs) in Participants With Obsessive-Compulsive Disorder (OCD) Phase 2 Interventional Hoffmann-La Roche