Discovery of potent indazole-based human glutaminyl cyclase (QC) inhibitors as Anti-Alzheimer's disease agents.

[1]  R. Priefer,et al.  Alzheimer's disease failed clinical trials. , 2022, Life sciences.

[2]  B. Roques,et al.  Molecular mechanisms in Alzheimer's disease and related potential treatments such as structural target convergence of antibodies and simple organic molecules. , 2022, European journal of medicinal chemistry.

[3]  M. Gold,et al.  Alzheimer’s Disease: Key Insights from Two Decades of Clinical Trial Failures , 2022, Journal of Alzheimer's disease : JAD.

[4]  S. Tatulian.  Challenges and hopes for Alzheimer's disease. , 2022, Drug discovery today.

[5]  T. Golde.  Disease-Modifying Therapies for Alzheimer’s Disease: More Questions than Answers , 2022, Neurotherapeutics.

[6]  Mina Esmail Zadeh Nojoo Kambar,et al.  Alzheimer's disease drug development pipeline: 2022 , 2022, Alzheimer's & dementia.

[7]  J. Rahfeld,et al.  Tetrahydroimidazo[4,5-c]pyridine-Based Inhibitors of Porphyromonas gingivalis Glutaminyl Cyclase , 2021, Pharmaceuticals.

[8]  P. Scheltens,et al.  Rationale and study design of a randomized, placebo-controlled, double-blind phase 2b trial to evaluate efficacy, safety, and tolerability of an oral glutaminyl cyclase inhibitor varoglutamstat (PQ912) in study participants with MCI and mild AD—VIVIAD , 2021, Alzheimer's research & therapy.

[9]  K. V. Dileep,et al.  Exploring the binding mode of PQ912 against secretory glutaminyl cyclase through systematic exploitation of conformational ensembles , 2021, Chemical biology & drug design.

[10]  Haiqiang Wu,et al.  Glutaminyl Cyclase, Diseases, and Development of Glutaminyl Cyclase Inhibitors. , 2021, Journal of medicinal chemistry.

[11]  Judite R M Coimbra,et al.  A patent review of glutaminyl cyclase inhibitors (2004–present) , 2021, Expert opinion on therapeutic patents.

[12]  Kam Y. J. Zhang,et al.  Piperidine-4-carboxamide as a new scaffold for designing secretory glutaminyl cyclase inhibitors. , 2020, International journal of biological macromolecules.

[13]  Blaine R. Roberts,et al.  Increased glutaminyl cyclase activity in brains of Alzheimer’s disease individuals , 2020, Journal of neurochemistry.

[14]  U. Diederichsen,et al.  Hydrazides are potent transition-state analogs for glutaminyl cyclase implicated in the pathogenesis of Alzheimer's Disease. , 2020, Biochemistry.

[15]  P. Moreira,et al.  An overview of glutaminyl cyclase inhibitors for Alzheimer's disease. , 2019, Future medicinal chemistry.

[16]  C. Stam,et al.  In pursuit of a sensitive EEG functional connectivity outcome measure for clinical trials in Alzheimer’s disease , 2019, Clinical Neurophysiology.

[17]  Kam Y. J. Zhang,et al.  Human Glutaminyl Cyclase: Structure, Function, Inhibitors and Involvement in Alzheimer's Disease. , 2019, Pharmacological research.

[18]  S. J. Y. Macalino,et al.  Discovery of Conformationally Restricted Human Glutaminyl Cyclase Inhibitors as Potent Anti-Alzheimer's Agents by Structure-Based Design. , 2019, Journal of medicinal chemistry.

[19]  P. Scheltens,et al.  Safety, tolerability and efficacy of the glutaminyl cyclase inhibitor PQ912 in Alzheimer’s disease: results of a randomized, double-blind, placebo-controlled phase 2a study , 2018, Alzheimer's Research & Therapy.

[20]  Wenjuan Wu,et al.  Identifying hQC Inhibitors of Alzheimer’s Disease by Effective Customized Pharmacophore-Based Virtual Screening, Molecular Dynamic Simulation, and Binding Free Energy Analysis , 2018, Applied Biochemistry and Biotechnology.

[21]  S. Mangani,et al.  The structure of the human glutaminyl cyclase–SEN177 complex indicates routes for developing new potent inhibitors as possible agents for the treatment of neurological disorders , 2018, JBIC Journal of Biological Inorganic Chemistry.

[22]  M. Cui,et al.  Structure-activity relationship investigation of Phe-Arg mimetic region of human glutaminyl cyclase inhibitors. , 2018, Bioorganic & medicinal chemistry.

[23]  M. Cui,et al.  Potent human glutaminyl cyclase inhibitors as potential anti-Alzheimer's agents: Structure-activity relationship study of Arg-mimetic region. , 2018, Bioorganic & medicinal chemistry.

[24]  Haiqiang Wu.  Can small molecule inhibitors of glutaminyl cyclase be used as a therapeutic for Alzheimer's disease? , 2017, Future medicinal chemistry.

[25]  Zhendan He,et al.  Synthesis and Evaluation of Diphenyl Conjugated Imidazole Derivatives as Potential Glutaminyl Cyclase Inhibitors for Treatment of Alzheimer's Disease. , 2017, Journal of medicinal chemistry.

[26]  T. Hoffmann,et al.  Glutaminyl Cyclase Inhibitor PQ912 Improves Cognition in Mouse Models of Alzheimer’s Disease—Studies on Relation to Effective Target Occupancy , 2017, The Journal of Pharmacology and Experimental Therapeutics.

[27]  M. Cui,et al.  Discovery of Potent Human Glutaminyl Cyclase Inhibitors as Anti-Alzheimer's Agents Based on Rational Design. , 2017, Journal of medicinal chemistry.

[28]  I. Simon,et al.  Identification of potential glutaminyl cyclase inhibitors from lead-like libraries by in silico and in vitro fragment-based screening , 2017, Molecular Diversity.

[29]  L. Wessjohann,et al.  Natural Products from Microalgae with Potential against Alzheimer’s Disease: Sulfolipids Are Potent Glutaminyl Cyclase Inhibitors , 2016, Marine drugs.

[30]  Zhendan He,et al.  Inhibitory effect of flavonoids on human glutaminyl cyclase. , 2016, Bioorganic & medicinal chemistry.

[31]  C. Hennekens,et al.  Hypothesis: glutaminyl cyclase inhibitors decrease risks of Alzheimer’s disease and related dementias , 2015, Expert review of neurotherapeutics.

[32]  F. Weber,et al.  A phase 1 study to evaluate the safety and pharmacokinetics of PQ912, a glutaminyl cyclase inhibitor, in healthy subjects , 2015, Alzheimer's & dementia.

[33]  Reinhard Schneider,et al.  siRNA screen identifies QPCT as a druggable target for Huntington’s disease , 2015, Nature chemical biology.

[34]  Oliver Wirths,et al.  Focusing the amyloid cascade hypothesis on N-truncated Abeta peptides as drug targets against Alzheimer’s disease , 2014, Acta Neuropathologica.

[35]  T. Hoffmann,et al.  Structure-activity relationships of benzimidazole-based glutaminyl cyclase inhibitors featuring a heteroaryl scaffold. , 2013, Journal of medicinal chemistry.

[36]  Jeewoo Lee,et al.  Structure-activity relationship of human glutaminyl cyclase inhibitors having an N-(5-methyl-1H-imidazol-1-yl)propyl thiourea template. , 2013, Bioorganic & medicinal chemistry.

[37]  Alexander G. Dossetter,et al.  Pharmacokinetic benefits of 3,4-dimethoxy substitution of a phenyl ring and design of isosteres yielding orally available cathepsin K inhibitors. , 2012, Journal of medicinal chemistry.

[38]  Hans-Ulrich Demuth,et al.  Prion-Like Behavior and Tau-dependent Cytotoxicity of Pyroglutamylated β-Amyloid , 2012, Nature.

[39]  T. Bayer,et al.  Pyroglutamate Amyloid-β (Aβ): A Hatchet Man in Alzheimer Disease* , 2011, The Journal of Biological Chemistry.

[40]  T. Bayer,et al.  Overexpression of Glutaminyl Cyclase, the Enzyme Responsible for Pyroglutamate Aβ Formation, Induces Behavioral Deficits, and Glutaminyl Cyclase Knock-out Rescues the Behavioral Phenotype in 5XFAD Mice* , 2010, The Journal of Biological Chemistry.

[41]  Hans-Ulrich Demuth,et al.  Inhibitors for human glutaminyl cyclase by structure based design and bioisosteric replacement. , 2009, Journal of medicinal chemistry.

[42]  Hans-Ulrich Demuth,et al.  Pyroglutamate formation influences solubility and amyloidogenicity of amyloid peptides. , 2009, Biochemistry.

[43]  Hans-Ulrich Demuth,et al.  Glutaminyl cyclase inhibition attenuates pyroglutamate Aβ and Alzheimer's disease–like pathology , 2008, Nature Medicine.

[44]  T. Hoffmann,et al.  Inhibition of glutaminyl cyclase prevents pGlu‐Aβ formation after intracortical/hippocampal microinjection in vivo/in situ , 2008, Journal of neurochemistry.

[45]  P. Carrupt,et al.  Parallel artificial membrane permeability assay: a new membrane for the fast prediction of passive human skin permeability. , 2006, Journal of medicinal chemistry.

[46]  Hans-Ulrich Demuth,et al.  The first potent inhibitors for human glutaminyl cyclase: synthesis and structure-activity relationship. , 2006, Journal of medicinal chemistry.

[47]  T. Kan,et al.  Preparation of Secondary Amines From Primary Amines Via 2‐Nitrobenzenesulfonamides: N‐(4‐Methoxybenzyl)‐3‐Phenylpropylamine , 2003 .

[48]  G. Damonte,et al.  Pyroglutamate‐modified amyloid β‐peptides – AβN3(pE) – strongly affect cultured neuron and astrocyte survival , 2002 .

[49]  T. Hoffmann,et al.  Continuous spectrometric assays for glutaminyl cyclase activity. , 2002, Analytical biochemistry.

[50]  C. Barrow,et al.  The Aβ 3-Pyroglutamyl and 11-Pyroglutamyl Peptides Found in Senile Plaque Have Greater β-Sheet Forming and Aggregation Propensities in Vitro than Full-Length Aβ† , 1999 .

[51]  M. Cheung,et al.  3- AND 4-NITROBENZENESULFONAMIDES : EXCEPTIONALLY VERSATILE MEANS FOR PREPARATION OF SECONDARY AMINES AND PROTECTION OF AMINES , 1995 .

[52]  D. Mann,et al.  Dominant and differential deposition of distinct β-amyloid peptide species, Aβ N3(pE), in senile plaques , 1995, Neuron.

[53]  T. Pohl,et al.  Primary structure and functional expression of a glutaminyl cyclase. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[54]  W. Busby,et al.  An enzyme(s) that converts glutaminyl-peptides into pyroglutamyl-peptides. Presence in pituitary, brain, adrenal medulla, and lymphocytes. , 1987, The Journal of biological chemistry.

[55]  W. Fischer,et al.  Identification of a mammalian glutaminyl cyclase converting glutaminyl into pyroglutamyl peptides. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[56]  T. Arendt,et al.  Glutaminyl cyclase in human cortex: correlation with (pGlu)-amyloid-β load and cognitive decline in Alzheimer's disease. , 2014, Journal of Alzheimer's disease : JAD.