Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C20H25ClN2O |
| Molecular Weight | 344.878 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCCN1C=CC(N2CCC(CC2)C3=CC=CC=C3)=C(Cl)C1=O
InChI
InChIKey=HYOGJHCDLQSAHX-UHFFFAOYSA-N
InChI=1S/C20H25ClN2O/c1-2-3-12-23-15-11-18(19(21)20(23)24)22-13-9-17(10-14-22)16-7-5-4-6-8-16/h4-8,11,15,17H,2-3,9-10,12-14H2,1H3
| Molecular Formula | C20H25ClN2O |
| Molecular Weight | 344.878 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionSources: http://adisinsight.springer.com/drugs/800030424http://www.addextherapeutics.com/rd/pipeline/adx71149-for-schizophrenia | https://www.ncbi.nlm.nih.gov/pubmed/25735992Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/25032784 | https://www.ncbi.nlm.nih.gov/pubmed/25692015 | https://www.ncbi.nlm.nih.gov/pubmed/25692027
Sources: http://adisinsight.springer.com/drugs/800030424http://www.addextherapeutics.com/rd/pipeline/adx71149-for-schizophrenia | https://www.ncbi.nlm.nih.gov/pubmed/25735992
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/25032784 | https://www.ncbi.nlm.nih.gov/pubmed/25692015 | https://www.ncbi.nlm.nih.gov/pubmed/25692027
JNJ-40411813 (aka ADX71149) is a metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulator (PAM) that has the potential to be the first oral non-dopaminergic drug that may address both the positive and negative symptoms of schizophrenia and other indications, such as anxiety. ADX71149 is differentiated from marketed antipsychotics in that it may also show efficacy on negative symptoms and avoid compliance-limiting side effects such as weight gain, hyperprolactinemia and extrapyramidal symptoms, which are associated with the use of dopamine antagonists. The development of ADX71149 is part of a worldwide research collaboration and license agreement between Addex and Janssen Pharmaceuticals, Inc. This drug was also investigated for use as an adjunctive treatment for major depressive disorder (MDD), however, these studies were discontinued. JNJ-40411813 is now in phase II clinical trial for the treatment of epilepsy.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: Q14416 Gene ID: 2912.0 Gene Symbol: GRM2 Target Organism: Homo sapiens (Human) |
147.0 nM [EC50] | ||
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
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| Palliative | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1246 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25735992 |
100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
JNJ-40411813 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
|
1750 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25735992 |
225 mg 2 times / day multiple, oral dose: 225 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
JNJ-40411813 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
789 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25735992 |
100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
JNJ-40411813 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
10150 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25735992 |
100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
JNJ-40411813 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
|
16191 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25735992 |
225 mg 2 times / day multiple, oral dose: 225 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
JNJ-40411813 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
6404 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25735992 |
100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
JNJ-40411813 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
29.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25735992 |
100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
JNJ-40411813 plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
|
34.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25735992 |
225 mg 2 times / day multiple, oral dose: 225 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
JNJ-40411813 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
24.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25735992 |
100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
JNJ-40411813 plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| inconclusive [IC50 12.9953 uM] | ||||
| no [IC50 >18 uM] | ||||
| no [IC50 >18 uM] | ||||
| no [IC50 >18 uM] | ||||
| yes [IC50 6 uM] | ||||
| yes [IC50 7 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| major | ||||
| yes |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| Preclinical evaluation of the antipsychotic potential of the mGlu2-positive allosteric modulator JNJ-40411813. | 2015 Mar |
|
| Translational neurophysiological markers for activity of the metabotropic glutamate receptor (mGluR2) modulator JNJ-40411813: Sleep EEG correlates in rodents and healthy men. | 2016 Apr |
|
| Efficacy and safety of an adjunctive mGlu2 receptor positive allosteric modulator to a SSRI/SNRI in anxious depression. | 2016 Jun 3 |
Patents
Sample Use Guides
Schizophrenia patients with residual negative symptoms would benefit most from treatment with ADX-71149 (JNJ-40411813), at a dose of 100 mg/day bid, as an adjunctive therapy to antipsychotics
Route of Administration:
Oral
JNJ-40411813 acts as a positive allosteric modulator at the cloned mGlu2 receptor: EC50 = 147 ± 42 nmol/L in a [(35)S]GTPγS binding assay with human metabotropic glutamate type 2 (hmGlu2) CHO cells and EC50 = 64 ± 29 nmol/L in a Ca(2+) mobilization assay with hmGlu2 G α16 cotransfected HEK293 cells.
| Substance Class |
Chemical
Created
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| Record UNII |
612BYT76F3
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| Record Status |
Validated (UNII)
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DTXSID601032323
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JNJ-40411813
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admin on Sat Dec 16 10:26:35 GMT 2023 , Edited by admin on Sat Dec 16 10:26:35 GMT 2023
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PRIMARY | Official Title: A Multicenter, Double-Blind, Placebo-Controlled Study of JNJ-40411813 as Adjunctive Treatment to an Antidepressant in Adults With Major Depressive Disorder With Anxiety SymptomsPurpose: The purpose of this study is to evaluate the efficacy and overall safety and tolerability of treatment with adjunctive JNJ-40411813 compared to placebo in patients with MDD with anxiety symptoms being treated with an antidepressant. | ||
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ADX-71149
Created by
admin on Sat Dec 16 10:26:35 GMT 2023 , Edited by admin on Sat Dec 16 10:26:35 GMT 2023
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PRIMARY | ADX-71149, also known as JNJ-4041183 and JNJ-mGluR2-PAM, is a selective positive allosteric modulator of the mGlu2 receptor. It is being studied by Addex Therapeutics and Janssen Pharmaceuticals for the treatment of schizophrenia. It was also researched by these companies for the treatment of anxious depression (major depressive disorder with anxiety symptoms), but although some efficacy was observed in clinical trials, it was not enough to warrant further development for this indication. As of 2015, ADX-71149 is in phase II clinical trials for schizophrenia. | ||
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TARGET->MODULATOR |
The pharmacokinetics and effects of JNJ-40411813 on cognition and subjective awareness were evaluated. Plasma JNJ-40411813 exposure was dose-dependent, t max ranged from 3-4 h and t 1/2 19.4-34.2 h across the dose levels. JNJ-40411813 significantly (p=0.02) reduced continuity of attention score (150 mg dose) and ameliorated smoking withdrawal-induced changes in power of attention and quality of episodic memory versus placebo. A modest reduction in alertness was observed at 150-225 mg doses, JNJ-40411813 (500 mg) reduced S(+) ketamine-induced negative symptoms by approximately 43% and 30% in cohorts 1 and 3, respectively. JNJ-40411813 was generally well-tolerated.
ALLOSTERIC ACTIVATOR
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| Related Record | Type | Details | ||
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ACTIVE MOIETY |
Originator: Addex Pharmaceuticals; Developer: Janssen Pharmaceuticals; Class: Antidepressant, Antipsychotic, Anxiolytic, Small molecule; Mechanism of Action: Metabotropic glutamate receptor 2 modulators; Highest Development Phases: Phase II for Major depressive disorder, Schizophrenia; Phase I for Psychiatric disorders; Most Recent Events: 22 Apr 2016 Chemical structure information added, 29 Jul 2015 Phase-II development is ongoing as adjunctive therapy for schizophrenia and for anxiety in major depressive disorder, 01 Nov 2013 Janssen completes a phase II trial in Major Depressive Disorder (adjunctive treatment in patients with anxiety symptoms) in Bulgaria, Hungary, Moldova, Romania, Russia and Ukraine (NCT01582815)
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