Lumateperone

Identification

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Name
Lumateperone
Accession Number
DB06077
Type
Small Molecule
Groups
Investigational
Description

Lumateperone (ITI-722/ITI-007) is a novel, first-in-class dual 5HT2A receptor antagonist/dopamine phosphoprotein modulator (DPPM) for schizophrenia. It is an orally available compound which combines potent 5HT2A receptor antagonism with cell-type-specific modulation of phosphoprotein pathways downstream of dopamine receptors. As of May 2015, Lumateperone is in phase III clinical trials for schizophrenia.

Structure
Thumb
Synonyms
Not Available
External IDs
ITI-722
Product Ingredients
IngredientUNIICASInChI Key
ITI-007JIE88N006O1187020-80-9LHAPOGAFBLSJJQ-GUTACTQSSA-N
Categories
UNII
70BSQ12069
CAS number
313368-91-1
Weight
Average: 393.506
Monoisotopic: 393.221640697
Chemical Formula
C24H28FN3O
InChI Key
HOIIHACBCFLJET-SFTDATJTSA-N
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/t20-,21-/m0/s1
IUPAC Name
1-(4-fluorophenyl)-4-[(10R,15S)-4-methyl-1,4,12-triazatetracyclo[7.6.1.0⁵,¹⁶.0¹⁰,¹⁵]hexadeca-5(16),6,8-trien-12-yl]butan-1-one
SMILES
[H][C@]12CCN(CCCC(=O)C3=CC=C(F)C=C3)C[C@@]1([H])C1=CC=CC3=C1N2CCN3C

Pharmacology

Indication

Investigated for use/treatment in schizophrenia and schizoaffective disorders.

Pharmacodynamics

Standard pharmacologic assays have confirmed ITI-007's partial agonist properties at the presynaptic dopamine D2 receptor and confirmed serotonin transporter antagonist activity which may be of added benefit to patients with schizoaffective disorder and other diseases associated with mood alterations. ITI-007 has a much lower propensity than several currently marketed antipsychotic drugs to bind receptors that mediate deleterious cardiovascular events, sedation and rapid and significant weight gain.

Mechanism of action

As a dopamine receptor phosphoprotein modulator (DPPM), ITI-007 has dual properties; it acts as a post-synaptic antagonist and as a pre-synaptic partial agonist. The combination of ITI-007's high-potency blockade of 5HT2A receptors and unique dopamine receptor activity will make it possible for the first time, to select a clinical dose capable of saturating 5HT2A receptors while permitting the "dialing in" of an optimal amount of dopamine receptor modulation. The ability to optimize the level of dopamine receptor modulation holds promise for the reduction of psychotic symptoms without incurring high levels of dopamine antagonism that cause motor disturbances and other deleterious side effects. In addition, the wide separation of affinity at 5HT2A and D2 receptors may allow for administration of the appropriate amount of dopamine modulation for antipsychotic maintenance therapy and the treatment of bipolar disorders.

TargetActionsOrganism
U5-hydroxytryptamine receptor 2ANot AvailableHumans
UD(2) dopamine receptorNot AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineLumateperone may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineLumateperone may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3,5-DinitrocatecholThe therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Lumateperone.
4-Bromo-2,5-dimethoxyamphetamineLumateperone may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Lumateperone.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Lumateperone is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Lumateperone.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Lumateperone is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AcepromazineThe risk or severity of adverse effects can be increased when Acepromazine is combined with Lumateperone.
AceprometazineThe risk or severity of adverse effects can be increased when Aceprometazine is combined with Lumateperone.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
21302490
PubChem Substance
310264860
ChemSpider
19328801
ChEMBL
CHEMBL3306803
Wikipedia
Lumateperone

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedBasic ScienceAlzheimer's Disease (AD)1
2CompletedBasic ScienceSchizophrenic Disorders1
2CompletedTreatmentSchizophrenic Disorders1
2RecruitingTreatmentSchizophrenic Disorders1
3Active Not RecruitingTreatmentDepression, Bipolar2
3CompletedTreatmentSchizophrenic Disorders2
3RecruitingTreatmentDepression, Bipolar1
3TerminatedTreatmentAgitation in Dementia, Including Alzheimer's Disease1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0805 mg/mLALOGPS
logP3.87ALOGPS
logP3.59ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)16.4ChemAxon
pKa (Strongest Basic)8.47ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area26.79 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity116.42 m3·mol-1ChemAxon
Polarizability43.08 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as alkyl-phenylketones. These are aromatic compounds containing a ketone substituted by one alkyl group, and a phenyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbonyl compounds
Direct Parent
Alkyl-phenylketones
Alternative Parents
Phenylbutylamines / Butyrophenones / Indoles and derivatives / Aryl alkyl ketones / Benzoyl derivatives / Dialkylarylamines / Aralkylamines / Fluorobenzenes / Piperidines / Aryl fluorides
show 7 more
Substituents
Alkyl-phenylketone / Butyrophenone / Phenylbutylamine / Indole or derivatives / Benzoyl / Tertiary aliphatic/aromatic amine / Dialkylarylamine / Aryl alkyl ketone / Fluorobenzene / Halobenzene
show 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da

Drug created on November 18, 2007 11:29 / Updated on June 04, 2019 06:21