Publications associées à Classical pharmacology

Artificial intelligence for natural product drug discovery

Philippe Schwaller, Florian Huber, Albert Hofstetter, Michael Alexander Skinnider

Developments in computational omics technologies have provided new means to access the hidden diversity of natural products, unearthing new potential for drug discovery. In parallel, artificial intelligence approaches such as machine learning have led to e ...

Nature Portfolio2023

Generating macrocyclic inhibitors of protein-protein interactions

Gontran Sangouard

Protein-protein interactions (PPIs) play important roles in many diseases and their modulation is an attractive strategy for developing new therapeutics. However, the relatively large and often flat binding surfaces of PPIs makes the development of inhibit ...

EPFL2022

Methods for the generation of large combinatorial macrocycle libraries

Sevan Mleh Habeshian

Macrocycles are an attractive class of molecules due to their good binding properties and yet rather small size that allows, in many cases, crossing membranes to reach intracellular targets. In comparison to classical small molecule drugs, macrocycles are ...

EPFL2021

A novel cell-based sensor detecting the activity of individual basic proprotein convertases

Daniel Constam, Karin Irmgard Löw, Stefan Kunz

The basic proprotein convertases (PCs) furin, PC1/3, PC2, PC5/6, PACE4, PC4, and PC7 are promising drug targets for human diseases. However, developing selective inhibitors remains challenging due to overlapping substrate recognition motifs and limited str ...

WILEY2019

A microfluidic array for high-content screening at whole-organism resolution

Johan Auwerx, Martinus Gijs, Matteo Cornaglia, Laurent Mouchiroud, Daniel Migliozzi

A main step for the development and the validation of medical drugs is the screening on whole organisms, which gives the systemic information that is missing when using cellular models. Among the organisms of choice, Caenorhabditis elegans is a soil worm w ...

SPIE-INT SOC OPTICAL ENGINEERING2018

Fluorescent Benzothiazinone Analogues Efficiently and Selectively Label Dpre1 in Mycobacteria and Actinobacteria

Paul Joseph Dyson, Stewart Cole, John McKinney, Neeraj Dhar, Thierry Laroche, Jérémie Piton, Joao Pedro De Almeida Neres, Raphael Christopher Sommer, Raju Mukherjee

Benzothiazinones (BTZ) are highly potent bactericidal inhibitors of mycobacteria and the lead compound, BTZ043, and the optimized drug candidate, PBTZ169, have potential for the treatment of tuberculosis. Here, we exploited the tractability of the BTZ scaf ...

2018

Development of an albumin-binding ligand for prolonging the plasma half-life of peptide therapeutics

Alessandro Zorzi

Peptides represent a promising format for the development of therapeutics since they combine the advantages of proteins and small molecules. Several techniques based on rational design or in vitro evolution can be used to develop peptides as therapeutics. ...

EPFL2017

The Inosine Monophosphate Dehydrogenase, GuaB2, Is a Vulnerable New Bactericidal Drug Target for Tuberculosis

Stewart Cole, John McKinney, Neeraj Dhar, Claudia Sala, Ruben Hartkoorn, Raphael Christopher Sommer, Anthony Vocat, Andréanne Lupien

VCC234718, a molecule with growth inhibitory activity against Mycobacterium tuberculosis (Mtb), was identified by phenotypic screening of a 15344-compound library. Sequencing of a VCC234718-resistant mutant identified a Y487C substitution in the inosine mo ...

Amer Chemical Soc2017

Inhibiting Mycobacterium tuberculosis within and without

Stewart Cole

Tuberculosis remains a scourge of global health with shrinking treatment options due to the spread of drug-resistant strains of Mycobacterium tuberculosis. Intensive efforts have been made in the past 15 years to find leads for drug development so that bet ...

Royal Soc2016

Allosteric Optical Control of a Class B G-Protein-Coupled Receptor

Johannes Broichhagen

Allosteric regulation promises to open up new therapeutic avenues by increasing drug specificity at G-protein-coupled receptors (GPCRs). However, drug discovery efforts are at present hampered by an inability to precisely control the allosteric site. Herei ...

Wiley-VCH Verlag GmbH2016

Encoded libraries of chemically modified peptides

Christian Heinis

The use of powerful technologies for generating and screening DNA-encoded protein libraries has helped drive the development of proteins as pharmaceutical ligands. However the development of peptides as pharmaceutical ligands has been more limited. Althoug ...

Elsevier2015

Next-generation antimicrobials: from chemical biology to first-in-class drugs

Paul Murima

The global emergence of multi-drug resistant bacteria invokes an urgent and imperative necessity for the identification of novel antimicrobials. The general lack of success in progressing novel chemical entities from target-based drug screens have prompted ...

Pharmaceutical Soc Korea2015

Thiophenecarboxamide Derivatives Activated by EthA Kill Mycobacterium tuberculosis by Inhibiting the CTP Synthetase PyrG

Stewart Cole, Ruben Hartkoorn

To combat the emergence of drug-resistant strains of Mycobacterium tuberculosis, new antitubercular agents and novel drug targets are needed. Phenotypic screening of a library of 594 hit compounds uncovered two leads that were active against M. tuberculosi ...

Elsevier2015

Lead selection and characterization of antitubercular compounds using the Nested Chemical Library

Stewart Cole, Ruben Hartkoorn, Edina Rita Székely

Discovering new drugs to treat tuberculosis more efficiently and to overcome multidrug resistance is a world health priority. To find novel antitubercular agents several approaches have been used in various institutions worldwide, including target-based ap ...

Elsevier2015

2-Carboxyquinoxalines Kill Mycobacterium tuberculosis through Noncovalent Inhibition of DprE1

Stewart Cole, Neeraj Dhar, Florence Pojer, Ruben Hartkoorn, Joao Pedro De Almeida Neres, Gaëlle Séraphine Kolly

Phenotypic screening of a quinoxaline library against replicating Mycobacterium tuberculosis led to the identification of lead compound Ty38c (3-((4-methoxybenzyl)amino)-6-(trifluoromethyl)quinoxaline-2-carboxylic acid). With an MIC99 and MBC of 3.1 mu M, ...

American Chemical Society2015

Establishment and Validation of Whole-Cell Based Fluorescence Assays to Identify Anti-Mycobacterial Compounds Using the Acanthamoeba castellanii - Mycobacterium marinum Host-Pathogen System

John McKinney, Hajer Ouertatani-Sakouhi, Thierry Soldati

Tuberculosis is considered to be one of the world's deadliest disease with 2 million deaths each year. The need for new antitubercular drugs is further exacerbated by the emergence of drug-resistance strains. Despite multiple recent efforts, the majority o ...

Public Library of Science2014

Abcb4 acts as multixenobiotic transporter and active barrier against chemical uptake in zebrafish (Danio rerio) embryos

Kristin Schirmer

Background: In mammals, ABCB1 constitutes a cellular "first line of defense" against a wide array of chemicals and drugs conferring cellular multidrug or multixenobiotic resistance (MDR/MXR). We tested the hypothesis that an ABCB1 ortholog serves as protec ...

Biomed Central Ltd2013

Label-Free Cytotoxicity Screening Assay by Digital Holographic Microscopy

Pierre Magistretti, Christian Depeursinge, Gerardo Turcatti, Benjamin Rappaz, Marc Chambon, Jonas Kühn, Etienne Shaffer, Jérôme Parent, Julien Mena

We introduce a label-free technology based on digital holographic microscopy (DHM) with applicability for screening by imaging, and we demonstrate its capability for cytotoxicity assessment using mammalian living cells. For this first high content screenin ...

Mary Ann Liebert2013

Endogenous Myc maintains the tumor microenvironment

Douglas Hanahan

The ubiquitous deregulation of Myc in human cancers makes it an intriguing therapeutic target, a notion supported by recent studies in Ras-driven lung tumors showing that inhibiting endogenous Myc triggers ubiquitous tumor regression. However, neither the ...

2011

Determining a receptor-ligand interaction useful in e.g. drug screening involves repetitive application of reversibly binding fluorescent ligands with fast association-dissociation kinetics

Horst Vogel, Rudolf Hovius, Jean-Manuel Segura, Marinela Gjoni Boillat, Christoph Schreiter

NOVELTY - Determining a receptor-ligand interaction involves repeatedly contacting a cell comprising a receptor, with a ligand, of the receptor in which the ligand has a fluorescence labeling group and binds reversibly to the receptor under conditions in w ...

2006