lumateperone   Click here for help

GtoPdb Ligand ID: 9099

Synonyms: Caplyta® | ITI-007
Approved drug
lumateperone is an approved drug (FDA (2019))
Compound class: Synthetic organic
Comment: Lumateperone (ITI-007) is an antipsychotic, with a novel mechanism of action, making it the first-in class agent of its type [2,5]. Note that the approved drug contains lumateperone tosylate (PubChem CID 44241743).
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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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Click here for structure editor
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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 0
Rotatable bonds 5
Topological polar surface area 26.79
Molecular weight 393.22
XLogP 4.26
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES Fc1ccc(cc1)C(=O)CCCN1CCC2C(C1)c1cccc3c1N2CCN3C
Isomeric SMILES Fc1ccc(cc1)C(=O)CCCN1CCC2C(C1)c1cccc3c1N2CCN3C
InChI InChI=1S/C24H28FN3O/c1-26-14-15-28-21-11-13-27(16-20(21)19-4-2-5-22(26)24(19)28)12-3-6-23(29)17-7-9-18(25)10-8-17/h2,4-5,7-10,20-21H,3,6,11-16H2,1H3
InChI Key HOIIHACBCFLJET-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
In Phase 1 and Phase 2 clinical trials, lumateperone demonstrated improved sleep maintenance, antipsychotic efficacy, and clinical signals consistent with reduction in negative symptoms associated with schizophrenia, depression and anxiety, and other symptoms associated with impaired social function. It was progressed to Phase 3 clinical trials for the treatment of schizophrenia, bipolar depression, and Alzheimer's disease [1]. Click here to link to ClinicalTrials.gov's full list of lumateperone trials. FDA approval as a treatment for schizophrenia was granted in December 2019.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Lumateperone simultaneously modulates serotonin, dopamine, and glutamate signalling, which are three neurotransmitter pathways that are implicated in severe mental illness. Low dose lumateperone behaves as a highly potent 5-HT2A receptor antagonist. As the dose is increased, engagement with additional molecular targets occurs with the compound showing modest dopamine receptor modulation and modest inhibition of serotonin transporters [4]. In relation to its effects on dopamine signalling via D2 receptors, lumateperone acts as a pre-synaptic partial agonist and post-synaptic antagonist.