Claudianne Lainé, Caroline De Witte, Alain Martoriati, Amaury Farce, Inès Metatla, Ida Chiara Guerrera, Katia Cailliau, Jamal Khalife, Christine Pierrot
International journal of molecular sciences
December 2025
Vol. 26(23)
The 26S proteasome is the main proteolytic machinery involved in protein degradation, thereby contributing to the homeostasis and stress response of eukaryotic cells. This macromolecular complex consists of a 20S core particle assembled with one or two 19S regulatory particles. Here, we describe the Plasmodium berghei (Pb) proteasome AAA-ATPase regulatory …
Emeline Charnelle, Alexandre Gobert, Romain Marteau, Maëla Pautric, Nicolas Renault, Aurélie Jonneaux, Darius Mazhari Dorooee, Amélie Laversin, Jean-Christophe Devedjian, Patricia Melnyk, Saïd Yous, David Devos, Raphaël Frédérick, Séverine Ravez, Jamal El Bakali
Journal of medicinal chemistry
August 2025
Vol. 68(15)Pages: 15766-15784
Ferroptosis, an iron-dependent regulated cell death, is implicated in several diseases, including cancer and neurodegeneration. While most ferroptosis inhibitors act as radical-trapping antioxidants, direct modulation of pro-ferroptotic enzymes remains underexplored. Acyl-coenzyme A synthetase long-chain family member 4 (ACSL4), a key regulator of ferroptosis, has emerged as a promising therapeutic target. …
Darius Mazhari Dorooee, Séverine Ravez, Didier Vertommen, Nicolas Renault, Nicolas Papadopoulos, Romain Marteau, Emeline Charnelle, Karine Porte, Alexandre Gobert, Nathalie Hennuyer, Gaetan Herinckx, Maëla Pautric, Aurélie Jonneaux, Jean Christophe Devedjian, David Devos, Bart Staels, Patricia Melnyk, Stefan N Constantinescu, Raphaël Frédérick, Jamal El Bakali
Angewandte Chemie (International ed. in English)
May 2025
Vol. 64(19)Pages: e202500518
Acyl-coenzyme A synthetase long-chain family member 4 (ACSL4), a pivotal enzyme in lipid metabolism, has emerged as a therapeutic target for ferroptosis-related conditions and cancer. However, its reference inhibitor, rosiglitazone, has off-target activity on peroxisome proliferator-activated receptor gamma (PPARγ), a key regulator of lipid homeostasis. Here, the discovery of LIBX-A401, …
Cellular and molecular life sciences : CMLS
March 2025
Vol. 82(1)Pages: 115
Some interstitial lung diseases involve pulmonary fibrosis, which is a process that is characterized by the excessive and abnormal accumulation of extracellular matrix in the pulmonary interalveolar space. Although the current anti-fibrotic therapy aims at slowing down the progression of pulmonary fibrosis, it does not reverse it, and many of …
Fanny Danton, Mohamed Othman, Ata Martin Lawson, Amaury Farce, Emmanuelle Lipka, Alina Ghinet, Ján Moncol, Abdelhabib Semlali, Adam Daïch
International journal of molecular sciences
February 2025
Vol. 26(4)
We report in this contribution the synthesis and in vitro biological evaluation of a novel class of chiral thiazoloisoindolinone scaffolds as potent inhibitors against human farnesyltransferase (FTase-h). The targeted products, sulfides (4), sulfoxides (5,6), and sulfones (7), containing up to three points of diversification, were obtained in a short-step sequence …
Andrew McGown, Nicolas Renault, Amélie Barczyk, Jordan Nafie, Luciano Barluzzi, Daniel Guest, Graham J Tizzard, Simon J Coles, David Leach, Daniel von Emloh, Léa Sutton, Kiera Bailey, Lewis Edmunds, Barnaby W Greenland, Régis Millet, John Spencer, Xavier Dezitter
ACS pharmacology & translational science
February 2025
Vol. 8(2)Pages: 446-459
The P2X purinergic receptor 7 (P2X7) has an essential role in inflammation, innate immunity, tumor progression, neurodegenerative diseases, and several other diseases, leading subsequently to the development of P2X7 modulators. AZ11645373 is a frequently studied P2X7 antagonist tool compound but always used as a racemic mixture. Racemic AZ11645373 can be …
Guillaume Patient, Corentin Bedart, Naim A Khan, Nicolas Renault, Amaury Farce
Molecular informatics
October 2024
Vol. 43(10)Pages: e202400046
FFA4 has gained interest in recent years since its deorphanization in 2005 and the characterization of the Free Fatty Acids receptors family for their therapeutic potential in metabolic disorders. The expression of FFA4 (also known as GPR120) in numerous organs throughout the human body makes this receptor a highly potent …
Aline Leconte, Justine Jacquin, Matthieu Duban, Caroline Deweer, Pauline Trapet, Frédéric Laruelle, Amaury Farce, Philippe Compère, Karin Sahmer, Valentin Fiévet, Alexis Hoste, Ali Siah, Anissa Lounès-Hadj Sahraoui, Philippe Jacques, François Coutte, Magali Deleu, Jérôme Muchembled
Microbiological research
September 2024
Vol. 286Pages: 127816
Apple scab, caused by the hemibiotrophic fungus Venturia inaequalis, is currently the most common and damaging disease in apple orchards. Two strains of V. inaequalis (S755 and Rs552) with different sensitivities to azole fungicides and the bacterial metabolite fengycin were compared to determine the mechanisms responsible for these differences. Antifungal …
Corentin Bedart, Grace Shimokura, Frederick G West, Tabitha E Wood, Robert A Batey, John J Irwin, Matthieu Schapira
Scientific data
June 2024
Vol. 11(1)Pages: 597
Computationally screening chemical libraries to discover molecules with desired properties is a common technique used in early-stage drug discovery. Recent progress in the field now enables the efficient exploration of billions of molecules within days or hours, but this exploration remains confined within the boundaries of the accessible chemistry space. …
Current opinion in structural biology
June 2024
Vol. 86Pages: 102812
Structure-based virtual screening can be a valuable approach to computationally select hit candidates based on their predicted interaction with a protein of interest. The recent explosion in the size of chemical libraries increases the chances of hitting high-quality compounds during virtual screening exercises but also poses new challenges as the …
Christian Bailly, Corentin Bedart, Gérard Vergoten
In silico pharmacology
January 2024
Vol. 12(1)Pages: 24
Tetraspanin CD81 is a transmembrane protein used as a co-receptor by different viruses and implicated in some cancer and inflammatory diseases. The design of therapeutic small molecules targeting CD81 lags behind monoclonal antibodies and peptides but different synthetic and natural products binding to CD81 have been identified. We have investigated …
Hala Mansour, Alejandro Cabezas-Cruz, Véronique Peucelle, Amaury Farce, Sophie Salomé-Desnoulez, Ines Metatla, Ida Chiara Guerrera, Thomas Hollin, Jamal Khalife
International journal of molecular sciences
August 2023
Vol. 24(16)
The Protein Phosphatase type 1 catalytic subunit (PP1c) (PF3D7_1414400) operates in combination with various regulatory proteins to specifically direct and control its phosphatase activity. However, there is little information about this phosphatase and its regulators in the human malaria parasite, Plasmodium falciparum. To address this knowledge gap, we conducted a …
Andreea Zubaș, Alina Ghinet, Amaury Farce, Joëlle Dubois, Elena Bîcu
Pharmaceuticals (Basel, Switzerland)
June 2023
Vol. 16(6)
In the search for innovative approaches to cancer chemotherapy, a chemical library of 49 cyanochalcones, 1a-r, 2a-o, and 3a-p, was designed as dual inhibitors of human farnesyltransferase (FTIs) and tubulin polymerization (MTIs) (FTIs/MTIs), two important biological targets in oncology. This approach is innovative since the same molecule would be able …
Karen Aknin, Alexis Bontemps, Amaury Farce, Eric Merlet, Philippe Belmont, Philippe Helissey, Philippe Chavatte, Marie-Agnès Sari, Sylviane Giorgi-Renault, Stéphanie Desbène-Finck
Journal of enzyme inhibition and medicinal chemistry
December 2022
Vol. 37(1)Pages: 252-268
New polycyclic heterocycles were synthesised and evaluated as potential inhibitors of thymidine phosphorylase (TP). Inspired by the pharmacophoric pyrimidinedione core of the natural substrate, four series have been designed in order to interact with large empty pockets of the active site: pyrimidoquinoline-2,4-diones (series A), pyrimidinedione linked to a pyrroloquinoline-1,3-diones (series …
Raphaël Bolteau, Romain Duroux, Amélie Laversin, Brandon Vreulz, Anna Shiriaeva, Benjamin Stauch, Gye Won Han, Vadim Cherezov, Nicolas Renault, Amélie Barczyk, Séverine Ravez, Mathilde Coevoet, Patricia Melnyk, Maxime Liberelle, Saïd Yous
European journal of medicinal chemistry
November 2022
Vol. 241Pages: 114620
The past fifty years have been marked by the surge of neurodegenerative diseases. Unfortunately, current treatments are only symptomatic. Hence, the search for new and innovative therapeutic targets for curative treatments becomes a major challenge. Among these targets, the adenosine A2A receptor (A2AAR) has been the subject of much research …
Christophe Mesangeau, Pascal Carato, Nicolas Renault, Mathilde Coevoet, Paul-Emmanuel Larchanché, Amélie Barczyk, Luc Buée, Nicolas Sergeant, Patricia Melnyk
International journal of molecular sciences
October 2022
Vol. 23(21)
The rationale to define the biological and molecular parameters derived from structure-activity relationships (SAR) is mandatory for the lead selection of small drug compounds. Several series of small molecules have been synthesized based on a computer-assisted pharmacophore design derived from two series of compounds whose scaffold originates from chloroquine or …
Marie Bobowski-Gerard, Clémence Boulet, Francesco P Zummo, Julie Dubois-Chevalier, Céline Gheeraert, Mohamed Bou Saleh, Jean-Marc Strub, Amaury Farce, Maheul Ploton, Loïc Guille, Jimmy Vandel, Antonino Bongiovanni, Ninon Very, Eloïse Woitrain, Audrey Deprince, Fanny Lalloyer, Eric Bauge, Lise Ferri, Line-Carolle Ntandja-Wandji, Alexia K Cotte, Corinne Grangette, Emmanuelle Vallez, Sarah Cianférani, Violeta Raverdy, Robert Caiazzo, Viviane Gnemmi, Emmanuelle Leteurtre, Benoit Pourcet, Réjane Paumelle, Kim Ravnskjaer, Guillaume Lassailly, Joel T Haas, Philippe Mathurin, François Pattou, Laurent Dubuquoy, Bart Staels, Philippe Lefebvre, Jérôme Eeckhoute
Nature communications
September 2022
Vol. 13(1)Pages: 5324
Tissue injury triggers activation of mesenchymal lineage cells into wound-repairing myofibroblasts, whose unrestrained activity leads to fibrosis. Although this process is largely controlled at the transcriptional level, whether the main transcription factors involved have all been identified has remained elusive. Here, we report multi-omics analyses unraveling Basonuclin 2 (BNC2) as …
Erika Cecon, Daniela Fernandois, Nicolas Renault, Caio Fernando Ferreira Coelho, Jan Wenzel, Corentin Bedart, Charlotte Izabelle, Sarah Gallet, Sophie Le Poder, Bernard Klonjkowski, Markus Schwaninger, Vincent Prevot, Julie Dam, Ralf Jockers
Cellular and molecular life sciences : CMLS
June 2022
Vol. 79(7)Pages: 361
COVID-19 is a complex disease with short- and long-term respiratory, inflammatory and neurological symptoms that are triggered by the infection with SARS-CoV-2. Invasion of the brain by SARS-CoV-2 has been observed in humans and is postulated to be involved in post-COVID state. Brain infection is particularly pronounced in the K18-hACE2 …
Raphaël Le Biannic, Romain Magnez, Frédérique Klupsch, Natascha Leleu-Chavain, Bryan Thiroux, Morgane Tardy, Hassiba El Bouazzati, Xavier Dezitter, Nicolas Renault, Gérard Vergoten, Christian Bailly, Bruno Quesnel, Xavier Thuru, Régis Millet
European journal of medicinal chemistry
June 2022
Vol. 236Pages: 114343
Immuno-therapy has become a leading strategy to fight cancer. Over the past few years, immuno-therapies using checkpoint inhibitor monoclonal antibodies (mAbs) against programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1) have demonstrated improved survival compared with chemotherapy. We describe the microwave-assisted synthesis and the characterization of an …
Maxime Liberelle, Florine Toulotte, Nicolas Renault, Muriel Gelin, Frédéric Allemand, Patricia Melnyk, Jean-François Guichou, Philippe Cotelle
Journal of medicinal chemistry
April 2022
Vol. 65(8)Pages: 5926-5940
The Hippo signaling pathway plays a fundamental role in the control of organ growth, cell proliferation, and stem cell characters. TEADs are the main transcriptional output regulators of the Hippo signaling pathway and bind to YAP and TAZ co-activators. TEAD1-4 are expressed differently, depending on the tissue and developmental level, …