Publications related to Monoamine oxidase inhibitor

An Oculus to Profile and Probe Target Engagement In Vivo: How T-REX Was Born and Its Evolution into G-REX

Here we provide a personal account of innovation and design principles underpinning a method to interrogate precision electrophile signaling that has come to be known as "REX technologies". This Account is framed in the context of trying to improve methods ...

AMER CHEMICAL SOC2021

Inhibition of Thiol‐Mediated Uptake with Irreversible Covalent Inhibitors

Jérôme Waser, Stefan Matile, Eliott Hugo Joran Le Du, Elija Grinhagena, Abhaya Kumar Mishra

Thiol-mediated uptake is emerging as method of choice to penetrate cells. This study focuses on irreversible covalent inhibitors of thiol-mediated uptake. High-content high-throughput screening of the so far largest collection of hypervalent iodine reagent ...

Wiley-VHCA AG2021

Novel irreversible covalent BTK inhibitors discovered using DNA-encoded chemistry

Sevan Mleh Habeshian, Ying Zhang

Libraries of DNA-Encoded small molecules created using combinatorial chemistry and synthetic oligonucleotides are being applied to drug discovery projects across the pharmaceutical industry. The majority of reported projects describe the discovery of rever ...

PERGAMON-ELSEVIER SCIENCE LTD2021

Safinamide inhibits in vivo glutamate release in a rat model of Parkinson's disease

Salvatore Novello

To investigate whether the reversible MAO-B inhibitor and sodium channel blocker safinamide impairs glutamate release under parkinsonian conditions in vivo, and this effect is dependent on MAO-B inhibition, safinamide (and rasagiline as a comparator) were ...

PERGAMON-ELSEVIER SCIENCE LTD2020

Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains

Florence Pojer, Kelvin Ka Ching Lau, Oliver Hantschel, Tim Kükenshöner, Grégory La Sala

The transcription factor STAT3 is frequently activated in human solid and hematological malignancies and remains a challenging therapeutic target with no approved drugs to date. Here, we develop synthetic antibody mimetics, termed monobodies, to interfere ...

Nature Research2020

Macrocycle synthesis strategy based on step-wise “adding and reacting” three components enables screening of large combinatorial libraries

Christian Heinis, Gerardo Turcatti, Julien Bortoli Chapalay, Alessandro Angelini, Alessandro Zorzi, Jonathan Patrice Vesin, Ganesh Kumar Mothukuri, Sangram Shivdas Kale, Kaycie Marie Butler, Carl Leonard Stenbratt

Macrocycles provide an attractive modality for drug development, but generating ligands for new targets is hampered by the limited availability of large macrocycle libraries. We have established a solution-phase macrocycle synthesis strategy in which three ...

2020

Dysfunction of homeostatic control of dopamine by astrocytes in the developing prefrontal cortex leads to cognitive impairments

Graham Knott, Corrado Cali, Nicole Déglon, Tamara Zehnder, Luca Pucci, Andrea Chicca

Astrocytes orchestrate neural development by powerfully coordinating synapse formation and function and, as such, may be critically involved in the pathogenesis of neurodevelopmental abnormalities and cognitive deficits commonly observed in psychiatric dis ...

2020

alpha-Synuclein O-GlcNAcylation alters aggregation and toxicity, revealing certain residues as potential inhibitors of Parkinson's disease

Hilal Lashuel, Anne-Laure Mahul Mellier

A compelling link is emerging between the posttranslational modification O-GlcNAc and protein aggregation. A prime example is alpha-synuclein, which forms toxic aggregates that are associated with neurodegeneration in Parkinson's and related diseases. alph ...

National Academy of Sciences2019

Arylvinylpiperazine Amides, a New Class of Potent Inhibitors Targeting QcrB of Mycobacterium tuberculosis

Stewart Cole, Andrej Benjak, Anthony Vocat, Jérémie Piton, Shi-Yan Caroline Foo, Andréanne Lupien, Raphael Christopher Sommer

New drugs are needed to control the current tuberculosis (TB) pandemic caused by infection with Mycobacterium tuberculosis. We report here on our work with AX-35, an arylvinylpiperazine amide, and four related analogs, which are potent antitubercular agent ...

AMER SOC MICROBIOLOGY2018

Synthesis and crystal structure of a chiral lactam and three amino alcohols as potential protein tyrosine phosphates 1B inhibitors

Rosario Scopelliti

Chiral lactam 2 and three chiral 3-amino alcohols 3-5 have been synthesized and characterized by Sspectroscopic techniques. Regioselective ring opening reaction of chiral styrene oxide by an amine nucle-ophile was confirmed by X-ray diffraction data. Ligan ...

Pergamon-Elsevier Science Ltd2017

Allosteric kinase inhibitors

Oliver Hantschel

Background. Inhibition of the kinase activity of the BCR-ABL1 oncoprotein by an allosteric mechanism of action facilitates alternative treatment options for chronic myeloid leukemia (CML) patients who cannot be adequately treated with conventional catalyti ...

Springer Nature2017

Discovery of a Selective Aurora A Kinase Inhibitor by Virtual Screening

Pierre Gönczy, Sachin Kotak, Maria Josefina Marcaida Lopez, Jean-Louis Reymond

Here we report the discovery of a selective inhibitor of Aurora A, a key regulator of cell division and potential anticancer target. We used the atom category extended ligand overlap score (xLOS), a 3D ligand-based virtual screening method recently develop ...

2016

Development of potent and selective S. aureus sortase A inhibitors Based on Peptide Macrocycles

Christian Heinis, Inmaculada Rentero Rebollo, Davide Bertoldo

Sortases are transpeptidase enzymes that anchor surface proteins, including virulence factors, to the cell wall of Gram-positive bacteria, and they are potential targets for the development of anti-infective agents. While several large compound libraries w ...

2016

A CMOS Amperometric System for Multi-Neurotransmitter Detection

Giovanni De Micheli, Sandro Carrara

In vivo multi-target and selective concentration monitoring of neurotransmitters can help to unravel the brain chemical complex signaling interplay. This paper presents a dedicated integrated potentiostat transducer circuit and its selective electrode inte ...

Ieee-Inst Electrical Electronics Engineers Inc2016

Optimization of the analogue-sensitive Cdc2/Cdk1 mutant by in vivo selection eliminates physiological limitations to its use in cell cycle analysis

Viesturs Simanis

Analogue-sensitive (as) mutants of kinases are widely used to selectively inhibit a single kinase with few off-target effects. The analogue-sensitive mutant cdc2-as of fission yeast (Schizosaccharomyces pombe) is a powerful tool to study the cell cycle, bu ...

Royal Society, The2014

4-Aminoquinolone Piperidine Amides: Noncovalent Inhibitors of DprE1 with Long Residence Time and Potent Antimycobacterial Activity

John McKinney, Neeraj Dhar, Joao Pedro De Almeida Neres, François Signorino-Gelo

4-Aminoquinolone piperidine amides (AQs) were identified as a novel scaffold starting from a whole cell screen, with potent cidality on Mycobacterium tuberculosis (Mtb). Evaluation of the minimum inhibitory concentrations, followed by whole genome sequenci ...

Amer Chemical Soc2014

MAOA-L carriers are better at making optimal financial decisions under risk

Genes can affect behaviour towards risks through at least two distinct neurocomputational mechanisms: they may affect the value assigned to different risky options, or they may affect the way in which the brain adjudicates between options based on their va ...

2011

Synthesis of novel pyrrolidine 3,4-diol derivatives as inhibitors of alpha-L-fucosidases

Pierre Vogel, Inmaculada Robina, Claudia Bello, Yolanda Vera-Ayoso

The stereoselective synthesis of new 3,4-dihydroxypyrrolidine derivatives starting from D-mannose, D-ribose and L-fucose is presented. Two synthetic strategies employing organometallic addition to hemiacetalic sugars followed by selective nucleophilic disp ...

2009

Intercellular calcium dynamics in smooth muscle cells : propagation of arterial vasomotion and influence of the endothelium

Dominique Seppey

Muscular arteries are able to actively modify their diameter by modulating the tone of the smooth muscle cells located within the arterial wall. A small variation of lumen diameter has a large influence on blood flow as well as on arterial pressure. The ca ...

EPFL2009

Mycobacterial Ser/Thr protein kinases and phosphatases: physiological roles and therapeutic potential

Stewart Cole, Pablo Fernandez

Reversible protein phosphorylation is a major regulation mechanism of fundamental biological processes, not only in eukaryotes but also in bacteria. A growing body of evidence suggests that Ser/Thr phosphorylation play important roles in the physiology and ...

2007