Delving into the Latest Updates on JNJ-39393406 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

CHRNA7

Action

modulators

Mechanism

α7 receptor modulators(Neuronal acetylcholine receptor protein alpha-7 subunit modulators)

Therapeutic Areas

Other Diseases

Active Indication

Tobacco Use Disorder

Inactive Indication

Alzheimer DiseaseCognition DisordersDepressive Disorder+ [3]

Originator Organization

Johnson & Johnson

Active Organization

Johnson & Johnson

National Institutes of HealthUniversity of Pittsburgh Medical Center

Inactive Organization

Janssen Pharmaceutica NVJohnson & Johnson Pharmaceutical Research & Development LLC

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC19H18F2N6O3

InChIKeyIURMHZBQEYNQOH-UHFFFAOYSA-N

CAS Registry953428-73-4

The study will assess a novel active drug vs. placebo on ability to reduce smoking and aid cessation during a one-week "practice" quit period for each condition in smokers with a high interest in quitting (i.e. crossover design). Medication effects on reducing withdrawal and cognitive impairment will help assess the mechanism to support quit smoking attempts.

Start Date01 Nov 2014

Sponsor / Collaborator

National Institutes of Health

100 Clinical Results associated with JNJ-39393406

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100 Translational Medicine associated with JNJ-39393406

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100 Patents (Medical) associated with JNJ-39393406

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7

Literatures (Medical) associated with JNJ-39393406

01 Oct 2021·European NeuropsychopharmacologyQ3 · MEDICINE

The effects of JNJ-39393406 a positive allosteric nicotine modulator on mood and cognition in patients with unipolar depression: A double-blind, add-on, placebo-controlled trial

Q3 · MEDICINE

Article

Author: Mark Weiser ; Carla Canuso ; Lisa Ford ; Igor Nastas ; John M. Davis ; Linda Levi ; Michael Davidson ; Jinyoung Park ; Stefanie Rassnick

Nicotinic agonists have been shown to improve cognition and mood, but this improvement is inconsistent and short-lived, possibly due to receptor desensitization. Positive Allosteric Modulators (PAMs) of the nicotinic alpha-7 nicotinic-acetyl-choline receptor (a7nAChR) are hypothesized to change the configuration of the nicotinic receptor and delay desensitization, potentially increasing the duration of the activation of the receptor, and improving clinical efficacy. This was a randomized controlled trial (RCT) adding JNJ-39393406 9 (a PAM of the a7nAChR) (n=35) or placebo (n=36) to treatment as usual for two weeks in 71 patients with unipolar depression. Mixed models for repeated measures analyses were performed Primary outcome measures were the Brief Assessment of Cognition in Schizophrenia (BACS) composite and the Montgomery-Asperg Depression Rating Scale (MADRS) scores. The drug was well tolerated, however mixed models for repeated measures comparing JNJ-39393406 to placebo showed no significant difference for MADRS total score (p=0.78), BACS composite score (p=0.34), or any of the secondary outcome measures. There was no significant difference in adverse events between the study groups (p=0.44). In conclusion, this study's findings do not support the hypothesis that a positive nicotinic receptor modulator can improve cognitive or depressive symptomatology in patients with unipolar depression.

01 Jan 2020·International Journal of PharmaceuticsQ2 · MEDICINE

Comparison of induction methods for supersaturation: pH shift versus solvent shift

Q2 · MEDICINE

Article

Author: Rades, Thomas ; Plum, Jakob ; Pérez-Alós, Laura ; Bavnhøj, Christoffer ; Palmelund, Henrik ; Müllertz, Anette

In order to investigate the supersaturation propensity of drugs in a simple and small-scale setup, induction of supersaturation is often performed via solvent shift. For weak bases, a potentially more biorelevant induction method would be a pH shift, as it is often hypothesized that the induction method will impact the supersaturation and precipitation. However, this has not been investigated systematically in a pharmaceutical context. This study investigates the impact of the induction method of supersaturation for nine basic drugs, A0619, A2853, albendazole, cinnarizine, dipyridamole, intraconazole, JNJ39393406, ketoconazole, and posaconazole, on four parameters: highest apparent degree of supersaturation, induction time, precipitation rate and solid form of the precipitate, using a novel standardized small-scale supersaturation and precipitation method. For eight of the nine drugs, the same highest apparent degree of supersaturation was obtained with both induction methods. For the induction time, precipitation rate and the solid form of the precipitate, no systematic differences between the induction methods were detected, however individual drugs did show differences. The study shows that, if a drug is sufficiently soluble at low pH, the solvent shift and pH shift induction methods of supersaturation yield comparable results.

01 Dec 2019·Stem Cell ResearchQ4 · MEDICINE

Alpha7 nicotinic acetylcholine receptors and neural network synaptic transmission in human induced pluripotent stem cell-derived neurons

Q4 · MEDICINE

ArticleOA

Author: Stummann, Tina C ; Hansen, Susanne K ; Larsen, Hjalte M ; Mikkelsen, Jens D ; Hyttel, Poul

The α7 nicotinic acetylcholine receptor has been extensively researched as a target for treatment of cognitive impairment in Alzheimer's disease and schizophrenia. Investigation of the α7 receptor is commonly performed in animals but it is critical to increase the biologically relevance of the model systems to fully capture the physiological role of the α7 receptor in humans. For example most humans, in contrast to animals, express the hybrid gene CHRFAM7A, the product of which modulates α7 receptor activity. In the present study, we used human induced pluripotent stem cell (hiPSC) derived neurons to establish a humanized α7 model. We established a cryobank of neural stem cells (NSCs) that could reproducibly be matured into neurons expressing neuronal markers and CHRNA7 and CHRFAM7A. The neurons responded to NMDA, GABA, and acetylcholine and exhibited synchronized spontaneous calcium oscillations. Gene expression studies and application of a range of α7 positive allosteric modulators (PNU-120595, TQS, JNJ-39393406 and AF58801) together with the α7 agonist PNU-282987 during measurement of intracellular calcium levels demonstrated the presence of functional α7 receptors in matured hiPSC-derived neuronal cultures. Pharmacological α7 activation also resulted in intracellular signaling as measured by ERK 1/2 phosphorylation and c-Fos protein expression. Moreover, PNU-120596 increased the frequency of the spontaneous calcium oscillations demonstrating implication of α7 receptors in human synaptic networks activity. Overall, we show that hiPSC derived neurons are an advanced in vitro model for studying human α7 receptor pharmacology and the involvement of this receptor in cellular processes as intracellular signaling and synaptic transmission.

100 Deals associated with JNJ-39393406

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11867

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Tobacco Use Disorder	Phase 2	-	National Institutes of Health	-
Tobacco Use Disorder	Phase 2	-	Johnson & Johnson	-
Tobacco Use Disorder	Phase 2	-	University of Pittsburgh Medical Center	-
Schizophrenia	Preclinical	United States	National Institutes of Health	01 Sep 2014
Cognition Disorders	Preclinical	Germany	Janssen Pharmaceutica NV	01 Aug 2009
Depressive Disorder	Discovery	Moldova	Johnson & Johnson Pharmaceutical Research & Development LLC	01 Feb 2016
Depressive Disorder	Discovery	Romania	Johnson & Johnson Pharmaceutical Research & Development LLC	01 Feb 2016
Schizoaffective disorder	Discovery	United States	National Institutes of Health	01 Sep 2014
Schizophrenia	Discovery	United States	National Institutes of Health	01 Sep 2014
Smoking Cessation	Discovery	United States	National Institutes of Health	01 Sep 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02230384 (TRENDS, CTgov)	Phase 2	Smoking Cessation \| Schizoaffective disorder \| Schizophrenia	62	Placebo Pill+Active JNJ Drug (Active JNJ Drug)	augcukxffb(nfmzkcrlll) = tkenuhnyna jkvblwxtii (vyzhettrnr, ntcinqcjtn - vchdqmgprr) View more	-	30 Jan 2018
				Placebo Pill+Active JNJ Drug (Placebo Pill)	augcukxffb(nfmzkcrlll) = jzquzcwjnj jkvblwxtii (vyzhettrnr, sjyhbuzapw - vcnqbztetl) View more