Delving into the Latest Updates on Ladostigil with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Ladostigil hemitartrate, Ladostigil tartrate, Ladostigil tartrate (USAN)

+ [2]

Target

MAO-A x MAO-B

Action

inhibitors

Mechanism

MAO-A inhibitors(Monoamine oxidase A inhibitors), MAO-B inhibitors(Monoamine oxidase B inhibitors)

Therapeutic Areas

Other Diseases

Active Indication

Cognitive Dysfunction

Inactive Indication

Alzheimer DiseaseAmnesiaDementia+ [1]

Originator Organization

Teva Pharmaceutical Industries Ltd.

Active Organization

Teva Pharmaceutical Industries Ltd.

Inactive Organization

Avraham Pharmaceuticals Ltd.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC20H26N2O8

InChIKeyDZMNQRCPJKPTNC-KBYGAXRISA-N

CAS Registry209394-46-7

View All Structures (2)

The purpose of this study is to determine whether treatment with the investigational drug ladostigil will delay the onset of Alzheimer's disease(AD) in patients with Mild Cognitive Impairment (MCI). MCI is now recognized as a precursor to AD and clinical tools are available to assess cognitive performance at this earlier stage. Ladostigil is currently under investigation for the treatment of AD. In this study, the investigators will be examining ladostigil at a lower dose level. At this dose level, ladostigil has been shown to reduce signs of early memory loss in animals. Thus, in this study the investigators are attempting to determine if earlier invention with a lower dose of ladostigil will significantly reduce initial memory loss and delay the subsequent progression to more serious cognitive dysfunction.

Start Date01 Feb 2012

Sponsor / Collaborator

Avraham Pharmaceuticals Ltd.

NCT01354691

/ CompletedPhase 2

A 6-Month Prospective, Multi-Center, Double-Blind, Placebo-Controlled, Randomized, Adaptive-Trial-Design Study to Evaluate the Safety and Efficacy of 80mg b.i.d Ladostigil in Patients With Mild to Moderate Probable Alzheimer's Disease

For many, Alzheimer's disease is the number one medical issue facing our aging society. It is a late onset neurodegenerative disease, frequently under diagnosed, that impairs memory and cognitive performance. There are no known treatments that can either prevent or reverse its progression. Consequently, there still remains a need to evaluate treatments which can better stabilize the symptoms of this disease. These symptoms frequently include decreased functional capacity and negative psychological attributes (e,g, depression, anxiety) in association with the memory and cognition deficits. This current study is being done to assess an investigational compound that has been designed to not only improved the cognitive status of affected patients but to also better manage all symptoms. Hence, the ultimate goal is to provide patients with an improved quality of life by slowing the progression of this neurodegenerative disease

Start Date01 Feb 2011

Sponsor / Collaborator

Avraham Pharmaceuticals Ltd.

EUCTR2010-019858-41-AT

/ Not yet recruitingNot Applicable

A 6-month prospective, multi-center, double-blind, placebo-controlled, randomized, adaptive-trial-design study to evaluate the safety and efficacy of 80mg b.i.d. ladostigil in patients with mild to moderate probable Alzheimer’s Disease with a 6-month open label follow-up period - CR100101/CO15570

Start Date25 Nov 2010

Sponsor / Collaborator

Avraham Pharmaceuticals Ltd.

100 Clinical Results associated with Ladostigil

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100 Translational Medicine associated with Ladostigil

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100 Patents (Medical) associated with Ladostigil

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83

Literatures (Medical) associated with Ladostigil

07 Dec 2022·ACS Chemical Neuroscience

Design, Synthesis, and Biological Evaluation of Novel Chromanone Derivatives as Multifunctional Agents for the Treatment of Alzheimer’s Disease

Article

Author: Yao, Hequan ; Zhou, Shengnan ; Allen, Stephanie ; White, Lisa ; Phillips, James ; Cheng, Feiyue ; Li, Xinnan ; Zhang, Bocheng ; Xu, Jinyi ; Lu, Li ; Li, Junda ; Li, Tiantian ; Jia, Yilin ; Zhu, Zheying ; Hu, Zhaoxin ; Zhan, Feiyan

Based on a multitarget strategy, a series of novel chromanone-1-benzyl-1,2,3,6-tetrahydropyridin hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation demonstrated that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B). The optimal compound C10 possessed excellent dual AChE/MAO-B inhibition both in terms of potency and equilibrium (AChE: IC₅₀ = 0.58 ± 0.05 μM; MAO-B: IC₅₀ = 0.41 ± 0.04 μM). Further molecular modeling and kinetic investigations revealed that compound C10 was a dual-binding inhibitor bound to both the catalytic anionic site and peripheral anionic site of AChE. In addition, compound C10 exhibited low neurotoxicity and potently inhibited AChE enzymatic activity. Furthermore, compound C10 more effectively protected against mitochondrial dysfunction and oxidation than donepezil, strongly inhibited AChE-induced amyloid aggregation, and moderately reduced glutaraldehyde-induced phosphorylation of tau protein in SH-SY5Y cells. Moreover, compound C10 displayed largely enhanced improvements in cognitive behaviors and spatial memory in a scopolamine-induced AD mice model with better efficacy than donepezil. Overall, the multifunctional profiles of compound C10 suggest that it deserves further investigation as a promising lead for the prospective treatment of AD.

27 Sep 2021·Zeitschrift für Naturforschung CQ4 · BIOLOGY

New indane derivatives containing 2-hydrazinothiazole as potential acetylcholinesterase and monoamine oxidase-B inhibitors

Q4 · BIOLOGY

Article

Author: Yurttaş, Leyla ; Ateş, İsmail Okan ; Sağlik, Begüm Nurpelin ; Evren, Asaf Evrim

AbstractAlthough radical treatment of Alzheimer’s and Parkinson’s disease is not possible yet, it is aimed to slow the course of the disease and increase the life quality of individuals with the drugs used in the clinic at the present time. Successful results have been achieved in the use of cholinesterase inhibitors and monoamine oxidase inhibitors together in these neurodegenerative diseases. In this study, indane ring which are in the structure of anticholinesterase effective molecules and 2-hydrazinothiazole structure whose inhibitory activities reported on monoamine oxidase-B (MAO-B) were combined; 4-(substituted phenyl)-2-[2-(3-phenyl-2,3-dihydro-1H-inden-1-ylidene) hydrazinyl]thiazole derivatives (3a–3i) were synthesized as dual inhibitors. The structures of the compounds were verified by IR, 1H-NMR, 13C-NMR, and HRMS spectroscopy. When enzyme inhibition activities were evaluated, it was determined that the compounds 3a (42.33%) and 3d (42.39%) on acetylcholinesterase (AChE) enzyme; compounds 3g (75.42%) and 3h (60.33%) showed inhibition on MAO-B enzyme at most, at 10−3 M concentration.

01 Aug 2021·Bioorganic ChemistryQ2 · CHEMISTRY

N-Propargylamine-hydroxypyridinone hybrids as multitarget agents for the treatment of Alzheimer’s disease

Q2 · CHEMISTRY

Article

Author: Zhong, Zhichao ; Jiang, Xiaoying ; Zhou, Tao ; Zhang, Yujia ; Xie, Yuanyuan ; Ge, Jiamin ; Guo, Jianan ; Zhang, Jingqi ; Bai, Renren ; Zhang, Changjun ; Yao, Chuansheng

AD is a progressive brain disorder. Because of the lack of remarkable single-target drugs against neurodegenerative disorders, the multitarget-directed ligand strategy has received attention as a promising therapeutic approach. Herein, we rationally designed twenty-nine hybrids of N-propargylamine-hydroxypyridinone. The designed hybrids possessed excellent iron-chelating activity (pFe³⁺ = 17.09-22.02) and potent monoamine oxidase B inhibitory effects. Various biological evaluations of the optimal compound 6b were performed step by step, including inhibition screening of monoamine oxidase (hMAO-B IC₅₀ = 0.083 ± 0.001 µM, hMAO-A IC₅₀ = 6.11 ± 0.08 µM; SI = 73.5), prediction of blood-brain barrier permeability and mouse behavioral research. All of these favorable results proved that the N-propargylamine-hydroxypyridinone scaffold is a promising structure for the discovery of multitargeted ligands for AD therapy.

100 Deals associated with Ladostigil

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External Link

KEGG	Wiki	ATC	Drug Bank
D03239	-	-	DB16213

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Phase 2	Serbia	Avraham Pharmaceuticals Ltd.	01 Feb 2011
Alzheimer Disease	Phase 2	Croatia	Avraham Pharmaceuticals Ltd.	01 Feb 2011
Alzheimer Disease	Phase 2	Germany	Avraham Pharmaceuticals Ltd.	01 Feb 2011
Alzheimer Disease	Phase 2	Spain	Avraham Pharmaceuticals Ltd.	01 Feb 2011
Alzheimer Disease	Phase 2	Austria	Avraham Pharmaceuticals Ltd.	01 Feb 2011
Amnesia	Phase 2	Germany	Avraham Pharmaceuticals Ltd.	01 Feb 2011
Amnesia	Phase 2	Austria	Avraham Pharmaceuticals Ltd.	01 Feb 2011
Amnesia	Phase 2	Serbia	Avraham Pharmaceuticals Ltd.	01 Feb 2011
Amnesia	Phase 2	Spain	Avraham Pharmaceuticals Ltd.	01 Feb 2011
Cognitive Dysfunction	Phase 2	-	Teva Pharmaceutical Industries Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01354691 (CTgov)	Phase 2	Alzheimer Disease \| Cognitive Dysfunction \| Amnesia	200	ladostigil hemitartrate (Ladostigil Hemitartrate)	vqhqkuvsxs(nczstvnmfa) = copkiflcei qxhnhqutmg (kddxdqkabe, rkjhjoxopk - jaywgsfluk) View more	-	30 Jul 2020
				ladostigil hemitartrate (Placebo)	vqhqkuvsxs(nczstvnmfa) = mxvslwqfvy qxhnhqutmg (kddxdqkabe, mnogxkssry - daugazsefs) View more
NCT01429623 (CTgov)	Phase 2	Mild cognitive disorder \| Dementia	210	ladostigil hemitartrate (Ladostigil Hemitartrate)	aqswoibjnt(jsuwiavizt) = jpbtwhwaqy yrolubirkd (fasmrjbodl, chpudzmiuq - inquybkmtg) View more	-	15 Jun 2017
				Placebo (Placebo Control)	aqswoibjnt(jsuwiavizt) = fiztkduytx yrolubirkd (fasmrjbodl, uouxzjnhnf - oflbaaectj) View more