Hydrazides Are Potent Transition-State Analogues for Glutaminyl Cyclase Implicated in the Pathogenesis of Alzheimer’s Disease

Biochemistry ◽  
2020 ◽  
Vol 59 (28) ◽  
pp. 2585-2591 ◽  
Author(s):  
Oliver Kupski ◽  
Lisa-Marie Funk ◽  
Viktor Sautner ◽  
Franziska Seifert ◽  
Brigitte Worbs ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transition State ◽  
Glutaminyl Cyclase ◽  
Transition State Analogues

Memapsin 2, a drug target for Alzheimer's disease

2003 ◽  
Vol 70 ◽  
pp. 213-220 ◽  
Author(s):  
Gerald Koelsch ◽  
Robert T. Turner ◽  
Lin Hong ◽  
Arun K. Ghosh ◽  
Jordan Tang
Keyword(s):  
Crystal Structure ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transition State ◽  
Amyloid Precursor Protein ◽  
Therapeutic Target ◽  
Drug Target ◽  
Aspartic Protease ◽  
Precursor Protein ◽  
Memapsin 2

Mempasin 2, a ϐ-secretase, is the membrane-anchored aspartic protease that initiates the cleavage of amyloid precursor protein leading to the production of ϐ-amyloid and the onset of Alzheimer's disease. Thus memapsin 2 is a major therapeutic target for the development of inhibitor drugs for the disease. Many biochemical tools, such as the specificity and crystal structure, have been established and have led to the design of potent and relatively small transition-state inhibitors. Although developing a clinically viable mempasin 2 inhibitor remains challenging, progress to date renders hope that memapsin 2 inhibitors may ultimately be useful for therapeutic reduction of ϐ-amyloid.

P3-031: New mouse model to develop and test drugs against the human Glutaminyl Cyclase (hQC) for Alzheimer's disease research

2011 ◽  
Vol 7 ◽  
pp. S524-S524
Author(s):  
Annamaria Molnar ◽  
Stephan Kurat ◽  
Stephan Schilling ◽  
Stefanie Flunkert ◽  
Hans Demuth ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Glutaminyl Cyclase ◽  
Disease Research

scholarly journals Natural Products from Microalgae with Potential against Alzheimer’s Disease: Sulfolipids Are Potent Glutaminyl Cyclase Inhibitors

Marine Drugs ◽  
2016 ◽  
Vol 14 (11) ◽  
pp. 203 ◽  
Author(s):  
Stephanie Hielscher-Michael ◽  
Carola Griehl ◽  
Mirko Buchholz ◽  
Hans-Ulrich Demuth ◽  
Norbert Arnold ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Glutaminyl Cyclase

The Development of Small Molecule Inhibitors of Glutaminyl Cyclase and Isoglutaminyl Cyclase for Alzheimer's Disease

2019 ◽  
Vol 4 (35) ◽  
pp. 10591-10600 ◽  
Author(s):  
Ana Xu ◽  
Feng He ◽  
Chenggong Yu ◽  
Ying Qu ◽  
Qiuqiong Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Glutaminyl Cyclase

2D- and 3D-QSAR Modeling of Imidazole-Based Glutaminyl Cyclase Inhibitors

2019 ◽  
Vol 15 ◽  
Author(s):  
Omar Husham Ahmed Al-Attraqchi ◽  
Katharigatta N. Venugopala
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Virtual Screening ◽  
Neurodegenerative Disorder ◽  
3D Qsar ◽  
Biological Evaluation ◽  
Qsar Modeling ◽  
Glutaminyl Cyclase ◽  
Validation Parameters ◽  
Qsar Models

Background: Glutaminyl cyclase (QC) is a novel target in the battle against Alzheimer’s disease, a highly prevalent neurodegenerative disorder. QC inhibitors have the potential to be developed as therapeutically useful anti-Alzheimer’s disease agents. Methods: Linear and non-linear 2D-quantitative structure–activity relationship (QSAR) models were developed using stepwise-multiple linear regression (S-MLR) and neural networks. Partial least squares (PLS) method was used to develop a 3D-QSAR model. Also, the developed models were used in a virtual screening of the ZINC database to identify potential QC inhibitors. Results: The 2D neural network model showed superior predictive ability, as demonstrated by the validation parameters R2 = 0.933, Q2 = 0.886 and R2pred = 0.911. The 3D-QSAR model’s steric and electrostatic fields’ isocontour maps were visualized and revealed important structural requirements associated with good activity. The virtual screening identified six compounds as potentially active QC inhibitors with improved pharmacokinetic profiles. Conclusion: The developed QSAR models can be used to predict the activity of compounds not yet synthesized and prioritize their synthesis and biological evaluation. Also, potentially active QC inhibitors have been identified with attractive lead-like properties that can be used to develop anti-Alzheimer’s disease agents.

Increased Glutaminyl Cyclase Expression in Peripheral Blood of Alzheimer's Disease Patients

2013 ◽  
Vol 34 (1) ◽  
pp. 263-271 ◽  
Author(s):  
Maria Teresa Valenti ◽  
Silvia Bolognin ◽  
Cristina Zanatta ◽  
Luca Donatelli ◽  
Giulio Innamorati ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Peripheral Blood ◽  
Glutaminyl Cyclase
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