Full Text Journal Articles by
Author Jana Janockova

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Huprine Y - Tryptophan heterodimers with potential implication to Alzheimer's disease treatment.

Eva Mezeiova, Martina Hrabinova, Vendula Hepnarova, Daniel Jun, Jana Janockova, Lubica Muckova, Lukas Prchal, Zdena Kristofikova, Tomas Kucera, Lukas Gorecki, Katarina Chalupova, Jiri Kunes, Jana Hroudova, Ondrej Soukup, Jan Korabecny,

The search for novel and effective therapeutics for Alzheimer's disease (AD) is the main quest that remains to be resolved. The goal is to find a disease-modifying agent able to confront the multifactorial nature of the disease positively. Herewith, a family of huprineY-tryptophan heterodimers was prepared, resulting in inhibition of ... Read more >>

Bioorg Med Chem Lett (Bioorganic & medicinal chemistry letters)
[2021, 43:128100]

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Phenothiazine-Tacrine Heterodimers: Pursuing Multitarget Directed Approach in Alzheimer's Disease.

Lukas Gorecki, Elisa Uliassi, Manuela Bartolini, Jana Janockova, Martina Hrabinova, Vendula Hepnarova, Lukas Prchal, Lubica Muckova, Jaroslav Pejchal, Jana Z Karasova, Eva Mezeiova, Marketa Benkova, Tereza Kobrlova, Ondrej Soukup, Sabrina Petralla, Barbara Monti, Jan Korabecny, Maria Laura Bolognesi,

Since 2002, no clinical candidate against Alzheimer's disease has reached the market; hence, an effective therapy is urgently needed. We followed the so-called "multitarget directed ligand" approach and designed 36 novel tacrine-phenothiazine heterodimers which were <i>in vitro</i> evaluated for their anticholinesterase properties. The assessment of the structure-activity relationships of such ... Read more >>

ACS Chem Neurosci (ACS chemical neuroscience)
[2021, 12(9):1698-1715]

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Synthesis of New Biscoumarin Derivatives, In Vitro Cholinesterase Inhibition, Molecular Modelling and Antiproliferative Effect in A549 Human Lung Carcinoma Cells.

Monika Hudáčová, Slávka Hamuľaková, Eva Konkoľová, Rastislav Jendželovský, Jana Vargová, Juraj Ševc, Peter Fedoročko, Ondrej Soukup, Jana Janočková, Veronika Ihnatova, Tomáš Kučera, Petr Bzonek, Nikola Novakova, Daniel Jun, Lucie Junova, Jan Korábečný, Kamil Kuča, Mária Kožurková,

A series of novel C4-C7-tethered biscoumarin derivatives (<b>12a</b>-<b>e</b>) linked through piperazine moiety was designed, synthesized, and evaluated biological/therapeutic potential. Biscoumarin <b>12d</b> was found to be the most effective inhibitor of both acetylcholinesterase (AChE, IC<sub>50</sub> = 6.30 µM) and butyrylcholinesterase (BChE, IC<sub>50</sub> = 49 µM). Detailed molecular modelling studies compared the ... Read more >>

Int J Mol Sci (International journal of molecular sciences)
[2021, 22(8):]

Cited: 1 time

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(±)-BIGI-3h: Pentatarget-Directed Ligand combining Cholinesterase, Monoamine Oxidase, and Glycogen Synthase Kinase 3β Inhibition with Calcium Channel Antagonism and Antiaggregating Properties for Alzheimer's Disease.

Lhassane Ismaili, Julie Monnin, Adeline Etievant, Raquel L Arribas, Lucía Viejo, Bernard Refouvelet, Ondrej Soukup, Jana Janockova, Vendula Hepnarova, Jan Korabecny, Tomas Kucera, Daniel Jun, Rudolf Andrys, Kamil Musilek, Aurelie Baguet, Eva M García-Frutos, Angela De Simone, Vincenza Andrisano, Manuela Bartolini, Cristóbal de Los Ríos, José Marco-Contelles, Emmanuel Haffen,

Multitarget-directed ligands (MTDLs) are considered a promising therapeutic strategy to address the multifactorial nature of Alzheimer's disease (AD). Novel MTDLs have been designed as inhibitors of human acetylcholinesterases/butyrylcholinesterases, monoamine oxidase A/B, and glycogen synthase kinase 3β and as calcium channel antagonists via the Biginelli multicomponent reaction. Among these MTDLs, (±)<b>-BIGI-3h</b> ... Read more >>

ACS Chem Neurosci (ACS chemical neuroscience)
[2021, 12(8):1328-1342]

Cited: 1 time

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Design and synthesis of novel tacrine-indole hybrids as potential multitarget-directed ligands for the treatment of Alzheimer's disease.

Slavka Hamulakova, Zuzana Kudlickova, Ladislav Janovec, Roman Mezencev, Zachery J Deckner, Yury O Chernoff, Jana Janockova, Veronika Ihnatova, Petr Bzonek, Nikola Novakova, Vendula Hepnarova, Martina Hrabinova, Daniel Jun, Jan Korabecny, Ondrej Soukup, Kamil Kuca,

The authors report on the synthesis and biological evaluation of new compounds whose structure combines tacrine and indole moieties. Tacrine-indole heterodimers were designed to inhibit cholinesterases and β-amyloid formation, and to cross the blood-brain barrier. The most potent new acetylcholinesterase inhibitors were compounds <b>3c</b> and <b>4d</b> (IC<sub>50</sub> = 25 and 39 nM, respectively). ... Read more >>

Future Med Chem (Future medicinal chemistry)
[2021, 13(9):785-804]

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2-Propargylamino-naphthoquinone derivatives as multipotent agents for the treatment of Alzheimer's disease.

Eva Mezeiova, Jana Janockova, Rudolf Andrys, Ondrej Soukup, Tereza Kobrlova, Lubica Muckova, Jaroslav Pejchal, Miriama Simunkova, Jiri Handl, Petra Micankova, Jan Capek, Tomas Rousar, Martina Hrabinova, Eugenie Nepovimova, Jose Luis Marco-Contelles, Marian Valko, Jan Korabecny,

Alzheimer's disease is a progressive brain disorder with characteristic symptoms and several pathological hallmarks. The concept of "one drug, one target" has not generated any new drugs since 2004. The new era of drug development in the field of AD builds upon rationally designed multi-target directed ligands that can better ... Read more >>

Eur J Med Chem (European journal of medicinal chemistry)
[2021, 211:113112]

Cited: 1 time

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Tacrine - Benzothiazoles: Novel class of potential multitarget anti-Alzheimeŕs drugs dealing with cholinergic, amyloid and mitochondrial systems.

Eugenie Nepovimova, Lucie Svobodova, Rafael Dolezal, Vendula Hepnarova, Lucie Junova, Daniel Jun, Jan Korabecny, Tomas Kucera, Zuzana Gazova, Katarina Motykova, Jana Kubackova, Zuzana Bednarikova, Jana Janockova, Catarina Jesus, Luisa Cortes, Joao Pina, Danijela Rostohar, Carlos Serpa, Ondrej Soukup, Laura Aitken, Rebecca E Hughes, Kamil Musilek, Lubica Muckova, Petr Jost, Marketa Chvojkova, Karel Vales, Martin Valis, Zofia Chrienova, Katarina Chalupova, Kamil Kuca,

A series of tacrine - benzothiazole hybrids incorporate inhibitors of acetylcholinesterase (AChE), amyloid β (Aβ) aggregation and mitochondrial enzyme ABAD, whose interaction with Aβ leads to mitochondrial dysfunction, into a single molecule. In vitro, several of 25 final compounds exerted excellent anti-AChE properties and interesting capabilities to block Aβ aggregation. ... Read more >>

Bioorg Chem (Bioorganic chemistry)
[2021, 107:104596]

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From orexin receptor agonist YNT-185 to novel antagonists with drug-like properties for the treatment of insomnia.

Eva Mezeiova, Jana Janockova, Jan Konecny, Tereza Kobrlova, Marketa Benkova, Rafael Dolezal, Lukas Prchal, Jana Karasova-Zdarova, Ondrej Soukup, Jan Korabecny,

YNT-185 is the first known small molecule acting as orexin 2 receptor (OX<sub>2</sub>R) agonist with implication to narcolepsy treatment, served as a template scaffold in generating a small set of seven compounds with predictive affinity to OX<sub>2</sub>R. The design of the new small molecules was driven mostly by improving physicochemical ... Read more >>

Bioorg Chem (Bioorganic chemistry)
[2020, 103:104179]

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Discovery of novel berberine derivatives with balanced cholinesterase and prolyl oligopeptidase inhibition profile.

Katerina Sobolova, Martina Hrabinova, Vendula Hepnarova, Tomas Kucera, Tereza Kobrlova, Marketa Benkova, Jana Janockova, Rafael Dolezal, Lukas Prchal, Ondrej Benek, Eva Mezeiova, Daniel Jun, Ondrej Soukup, Jan Korabecny,

Berberine, a naturally occurring compound, possesses an interesting multipotent pharmacological profile potentially applicable for Alzheimer's disease (AD) treatment. In this study, a series of novel 22 berberine derivatives was developed and tested in vitro. Berberine core was substituted at position 9-O of its aromatic ring region. All the hybrids under the ... Read more >>

Eur J Med Chem (European journal of medicinal chemistry)
[2020, 203:112593]

Cited: 4 times

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Synthesis and biological assessment of KojoTacrines as new agents for Alzheimer's disease therapy.

Youssef Dgachi, Hélène Martin, Rim Malek, Daniel Jun, Jana Janockova, Vendula Sepsova, Ondrej Soukup, Isabel Iriepa, Ignacio Moraleda, Emna Maalej, M Carmo Carreiras, Bernard Refouvelet, Fakher Chabchoub, José Marco-Contelles, Lhassane Ismaili,

In view of the multifactorial nature of Alzheimer's disease (AD), multitarget small molecules (MTSM) represent the most potent and attractive therapeutic strategy to design new drugs for Alzheimer's disease therapy. The new MTSM KojoTacrines (KTs) were designed and synthesized by juxtaposition of selected pharmacophoric motifs from kojic acid and tacrine. ... Read more >>

J Enzyme Inhib Med Chem (Journal of enzyme inhibition and medicinal chemistry)
[2019, 34(1):163-170]

Cited: 2 times

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Search for multifunctional agents against Alzheimer's disease among non-imidazole histamine H3 receptor ligands. In vitro and in vivo pharmacological evaluation and computational studies of piperazine derivatives.

Jakub Jończyk, Krzysztof Lodarski, Marek Staszewski, Justyna Godyń, Paula Zaręba, Ondrej Soukup, Jana Janockova, Jan Korabecny, Kinga Sałat, Natalia Malikowska-Racia, Michalina Hebda, Natalia Szałaj, Barbara Filipek, Krzysztof Walczyński, Barbara Malawska, Marek Bajda,

In the search for new treatments for complex disorders such as Alzheimer's disease the Multi-Target-Directed Ligands represent a very promising approach. The aim of the present study was to identify multifunctional compounds among several series of non-imidazole histamine H3 receptor ligands, derivatives of 1-[2-thiazol-5-yl-(2-aminoethyl)]-4-n-propylpiperazine, 1-[2-thiazol-4-yl-(2-aminoethyl)]-4-n-propylpiperazine and 1-phenoxyalkyl-4-(amino)alkylopiperazine using in vitro ... Read more >>

Bioorg Chem (Bioorganic chemistry)
[2019, 90:103084]

Cited: 2 times

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Profiling donepezil template into multipotent hybrids with antioxidant properties.

Eva Mezeiova, Katarina Spilovska, Eugenie Nepovimova, Lukas Gorecki, Ondrej Soukup, Rafael Dolezal, David Malinak, Jana Janockova, Daniel Jun, Kamil Kuca, Jan Korabecny,

Alzheimer's disease is debilitating neurodegenerative disorder in the elderly. Current therapy relies on administration of acetylcholinesterase inhibitors (AChEIs) -donepezil, rivastigmine, galantamine, and N-methyl-d-aspartate receptor antagonist memantine. However, their therapeutic effect is only short-term and stabilizes cognitive functions for up to 2 years. Given this drawback together with other pathological hallmarks ... Read more >>

J Enzyme Inhib Med Chem (Journal of enzyme inhibition and medicinal chemistry)
[2018, 33(1):583-606]

Cited: 12 times

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Orexin supplementation in narcolepsy treatment: A review.

Eugenie Nepovimova, Jana Janockova, Jan Misik, Stepan Kubik, Ales Stuchlik, Karel Vales, Jan Korabecny, Eva Mezeiova, Rafael Dolezal, Ondrej Soukup, Tereza Kobrlova, Ngoc Lam Pham, Thuy Duong Nguyen, Jan Konecny, Kamil Kuca,

Narcolepsy is a rare, chronic neurological disease characterized by excessive daytime sleepiness, cataplexy, vivid hallucinations, and sleep paralysis. Narcolepsy occurs in approximately 1 of 3000 people, affecting mainly adolescents aged 15 to 30 years. Recently, people with narcolepsy were shown to exhibit extensive orexin/hypocretin neuronal loss. The orexin system regulates ... Read more >>

Med Res Rev (Medicinal research reviews)
[2019, 39(3):961-975]

Cited: 7 times

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Tackling neuroinflammation and cholinergic deficit in Alzheimer's disease: Multi-target inhibitors of cholinesterases, cyclooxygenase-2 and 15-lipoxygenase.

Ehab D AlFadly, Perihan A Elzahhar, Anna Tramarin, Salwa Elkazaz, Hossam Shaltout, Marwa M Abu-Serie, Jana Janockova, Ondrej Soukup, Doaa A Ghareeb, Ahmed F El-Yazbi, Rim W Rafeh, Nour-Mounira Z Bakkar, Firas Kobeissy, Isabel Iriepa, Ignacio Moraleda, Manal N S Saudi, Manuela Bartolini, Ahmed S F Belal,

Neuroinflammation and cholinergic deficit are key detrimental processes involved in Alzheimer's disease. Hence, in the search for novel and effective treatment strategies, the multi-target-directed ligand paradigm was applied to the rational design of two series of new hybrids endowed with anti-inflammatory and anticholinesterase activity via triple targeting properties, namely able ... Read more >>

Eur J Med Chem (European journal of medicinal chemistry)
[2019, 167:161-186]

Cited: 7 times

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Investigation of New Orexin 2 Receptor Modulators Using In Silico and In Vitro Methods.

Jana Janockova, Rafael Dolezal, Eugenie Nepovimova, Tereza Kobrlova, Marketa Benkova, Kamil Kuca, Jan Konecny, Eva Mezeiova, Michaela Melikova, Vendula Hepnarova, Avi Ring, Ondrej Soukup, Jan Korabecny,

The neuropeptides, orexin A and orexin B (also known as hypocretins), are produced in hypothalamic neurons and belong to ligands for orphan G protein-coupled receptors. Generally, the primary role of orexins is to act as excitatory neurotransmitters and regulate the sleep process. Lack of orexins may lead to sleep disorder ... Read more >>

Molecules (Molecules (Basel, Switzerland))
[2018, 23(11):]

Cited: 1 time

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N-alkylated Tacrine Derivatives as Potential Agents in Alzheimer's Disease Therapy.

Eugenie Nepovimova, Jan Korabecny, Vendula Hepnarova, Daniel Jun, Rafael Dolezal, Lubica Muckova, Petr Jost, Ondrej Soukup, Jana Janockova, Ngoc Lam Pham, Thuy Duong Nguyen, Martin Valis, Kamil Kuca,

<h4>Background</h4>Based on the prevalence studies, the number of people suffering from dementia will almost double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050, assuming no changes in mortality, effective preventative measures, definitive diagnostic guidelines or curative treatment. From the abovementioned epidemiological data, it is obvious ... Read more >>

Curr Alzheimer Res (Current Alzheimer research)
[2019, 16(4):333-343]

Cited: 1 time

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Proliferation inhibition of novel diphenylamine derivatives.

Ladislav Janovec, Jana Janočková, Mária Matejová, Eva Konkoľová, Helena Paulíková, Daniela Lichancová, Lenka Júnošová, Slávka Hamuľaková, Ján Imrich, Mária Kožurková,

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used drugs in the world but some NSAIDs such as diclofenac and tolfenamic acid display levels of cytotoxicity, an effect which has been attributed to the presence of diphenylamine contained in their structures. A novel series of diphenylamine derivatives were synthetised and ... Read more >>

Bioorg Chem (Bioorganic chemistry)
[2019, 83:487-499]

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Rational design of novel TLR4 ligands by in silico screening and their functional and structural characterization in vitro.

Jan Honegr, David Malinak, Rafael Dolezal, Ondrej Soukup, Marketa Benkova, Lukas Hroch, Ondrej Benek, Jana Janockova, Kamil Kuca, Roman Prymula,

The purpose of this study was to identify new small molecules that possess activity on human toll-like receptor 4 associated with the myeloid differentiation protein 2 (hTLR4/MD2). Following current rational drug design principles, we firstly performed a ligand and structure based virtual screening of more than 130 000 compounds to discover ... Read more >>

Eur J Med Chem (European journal of medicinal chemistry)
[2018, 146:38-46]

Cited: 3 times

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Tacrine-coumarin and Tacrine-7-chloroquinoline Hybrids with Thiourea Linkers: Cholinesterase Inhibition Properties, Kinetic Study, Molecular Docking and Permeability Assay for Blood-brain Barrier.

Slavka Hamulakova, Ladislav Janovec, Ondrej Soukup, Daniel Jun, Jana Janockova, Martina Hrabinova, Vendula Sepsova, Kamil Kuca,

<h4>Background</h4>The design of new heterodimeric dual binding site acetylcholinesterase inhibitors constitutes the main goal-directed to the development of new anticholinesterase agents with the expanded pharmacological profile. Multi-target compounds are usually designed by combining in a hybrid molecule with two or more pharmacophoric moieties that are known to enable interaction with ... Read more >>

Curr Alzheimer Res (Current Alzheimer research)
[2018, 15(12):1096-1105]

Cited: 1 time

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Multitarget-Directed Ligands Combining Cholinesterase and Monoamine Oxidase Inhibition with Histamine H3 R Antagonism for Neurodegenerative Diseases.

Óscar M Bautista-Aguilera, Stefanie Hagenow, Alejandra Palomino-Antolin, Víctor Farré-Alins, Lhassane Ismaili, Pierre-Louis Joffrin, María L Jimeno, Ondřej Soukup, Jana Janočková, Lena Kalinowsky, Ewgenij Proschak, Isabel Iriepa, Ignacio Moraleda, Johannes S Schwed, Alejandro Romero Martínez, Francisco López-Muñoz, Mourad Chioua, Javier Egea, Rona R Ramsay, José Marco-Contelles, Holger Stark,

The therapy of complex neurodegenerative diseases requires the development of multitarget-directed drugs (MTDs). Novel indole derivatives with inhibitory activity towards acetyl/butyrylcholinesterases and monoamine oxidases A/B as well as the histamine H<sub>3</sub> receptor (H3R) were obtained by optimization of the neuroprotectant ASS234 by incorporating generally accepted H3R pharmacophore motifs. These small-molecule ... Read more >>

Angew Chem Int Ed Engl (Angewandte Chemie (International ed. in English))
[2017, 56(41):12765-12769]

Cited: 18 times

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Synthesis and evaluation of frentizole-based indolyl thiourea analogues as MAO/ABAD inhibitors for Alzheimer's disease treatment.

Lukas Hroch, Patrick Guest, Ondrej Benek, Ondrej Soukup, Jana Janockova, Rafael Dolezal, Kamil Kuca, Laura Aitken, Terry K Smith, Frank Gunn-Moore, Dominykas Zala, Rona R Ramsay, Kamil Musilek,

Alzheimer's disease (AD) is a neurodegenerative disorder associated with an excessive accumulation of amyloid-beta peptide (Aβ). Based on the multifactorial nature of AD, preparation of multi-target-directed ligands presents a viable option to address more pathological events at one time. A novel class of asymmetrical disubstituted indolyl thioureas have been designed ... Read more >>

Bioorg Med Chem (Bioorganic & medicinal chemistry)
[2017, 25(3):1143-1152]

Cited: 11 times

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The Antioxidant Additive Approach for Alzheimer's Disease Therapy: New Ferulic (Lipoic) Acid Plus Melatonin Modified Tacrines as Cholinesterases Inhibitors, Direct Antioxidants, and Nuclear Factor (Erythroid-Derived 2)-Like 2 Activators.

Mohamed Benchekroun, Alejandro Romero, Javier Egea, Rafael León, Patrycja Michalska, Izaskun Buendía, María Luisa Jimeno, Daniel Jun, Jana Janockova, Vendula Sepsova, Ondrej Soukup, Oscar M Bautista-Aguilera, Bernard Refouvelet, Olivier Ouari, José Marco-Contelles, Lhassane Ismaili,

Novel multifunctional tacrines for Alzheimer's disease were obtained by Ugi-reaction between ferulic (or lipoic acid), a melatonin-like isocyanide, formaldehyde, and tacrine derivatives, according to the antioxidant additive approach in order to modulate the oxidative stress as therapeutic strategy. Compound 5c has been identified as a promising permeable agent showing excellent ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2016, 59(21):9967-9973]

Cited: 20 times

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Design, synthesis and biological evaluation of new phthalimide and saccharin derivatives with alicyclic amines targeting cholinesterases, beta-secretase and amyloid beta aggregation.

Dawid Panek, Anna Więckowska, Tomasz Wichur, Marek Bajda, Justyna Godyń, Jakub Jończyk, Kamil Mika, Jana Janockova, Ondrej Soukup, Damijan Knez, Jan Korabecny, Stanislav Gobec, Barbara Malawska,

The complexity of Alzheimer's disease (AD) calls for search of multifunctional compounds as potential candidates for effective therapy. A series of phthalimide and saccharin derivatives linked by different alicyclic fragments (piperazine, hexahydropyrimidine, 3-aminopyrrolidine or 3-aminopiperidine) with phenylalkyl moieties attached have been designed, synthesized, and evaluated as multifunctional anti-AD agents with ... Read more >>

Eur J Med Chem (European journal of medicinal chemistry)
[2017, 125:676-695]

Cited: 18 times

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Tetrahydropyranodiquinolin-8-amines as new, non hepatotoxic, antioxidant, and acetylcholinesterase inhibitors for Alzheimer's disease therapy.

Youssef Dgachi, Olga Sokolov, Vincent Luzet, Justyna Godyń, Dawid Panek, Alexandre Bonet, Hélène Martin, Isabel Iriepa, Ignacio Moraleda, Cristina García-Iriepa, Jana Janockova, Lysiane Richert, Ondrej Soukup, Barbara Malawska, Fakher Chabchoub, José Marco-Contelles, Lhassane Ismaili,

Herein we report an efficient two step synthesis and biological assessment of 12 racemic tetrahydropyranodiquinolin-8-amines derivatives as antioxidant, cholinesterase inhibitors and non-hepatotoxic agents. Based on the results of the primary screening, we identified 7-(3-methoxyphenyl)-9,10,11,12-tetrahydro-7H-pyrano[2,3-b:5,6-h']diquinolin-8-amine (2h) as a particularly interesting non-hepatotoxic compound that shows moderate antioxidant activity (1.83 equiv Trolox in ... Read more >>

Eur J Med Chem (European journal of medicinal chemistry)
[2017, 126:576-589]

Cited: 7 times

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Design, synthesis and in vitro evaluation of benzothiazole-based ureas as potential ABAD/17β-HSD10 modulators for Alzheimer's disease treatment.

Lukas Hroch, Ondrej Benek, Patrick Guest, Laura Aitken, Ondrej Soukup, Jana Janockova, Karel Musil, Vlastimil Dohnal, Rafael Dolezal, Kamil Kuca, Terry K Smith, Frank Gunn-Moore, Kamil Musilek,

Amyloid-beta peptide (Aβ) has been recognized to interact with numerous proteins, which may lead to pathological changes in cell metabolism of Alzheimer's disease (AD) patients. One such known metabolic enzyme is mitochondrial amyloid-binding alcohol dehydrogenase (ABAD), also known as 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10). Altered enzyme function caused by the ... Read more >>

Bioorg Med Chem Lett (Bioorganic & medicinal chemistry letters)
[2016, 26(15):3675-3678]

Cited: 6 times

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