Article
Respiratory System
Laurent Meijer, Genevieve Hery-Arnaud, Cyril Leven, Emmanuel Nowak, Sophie Hillion, Yves Renaudineau, Isabelle Durieu, Raphael Chiron, Anne Prevotat, Isabelle Fajac, Dominique Hubert, Marlene Murris-Espin, Sandrine Huge, Isabelle Danner-Boucher, Bruno Ravoninjatovo, Sylvie Leroy, Julie Macey, Thierry Urban, Gilles Rault, Dominique Mottier, Rozenn Le Berre
Summary: A study was conducted to evaluate the safety and effects of roscovitine in patients with Cushing disease. The results showed that roscovitine was relatively safe and well-tolerated, but did not show significant efficacy in treating the disease. The variability in pharmacokinetics of roscovitine may have contributed to the lack of effectiveness.
JOURNAL OF CYSTIC FIBROSIS
(2022)
Article
Chemistry, Medicinal
Tania Tahtouh, Emilie Durieu, Benoit Villiers, Celine Bruyere, Thu Lan Nguyen, Xavier Fant, Kwang H. Ahn, Leepakshi Khurana, Emmanuel Deau, Mattias F. Lindberg, Elodie Severe, Frederic Miege, Didier Roche, Emmanuelle Limanton, Jean-Martial L'helgoual'ch, Guillaume Burgy, Solene Guiheneuf, Yann Herault, Debra A. Kendall, Francois Carreaux, Jean-Pierre Bazureau, Laurent Meijer
Summary: Leucettines, derived from marine sponge alkaloid Leucettamine B, have potential therapeutic applications for Alzheimer's disease, Down syndrome, diabetes, and other diseases. There is a correlation between the inhibition of specific kinase targets and cellular effects.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Wael Zeinyeh, Yannick J. Esvan, Beatrice Josselin, Mathilde Defois, Blandine Baratte, Stefan Knapp, Apirat Chaikuad, Fabrice Anizon, Francis Giraud, Sandrine Ruchaud, Pascale Moreau
Summary: Haspin is a potential target for the development of anticancer drugs, but current inhibitors show poor selectivity for human kinome. A new inhibitor with excellent activity and selectivity for Haspin has been identified, and its binding mode with Haspin has been determined through crystallography.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Endocrinology & Metabolism
Mythily Ganapathi, Gaelle Friocourt, Naig Gueguen, Marisa W. Friederich, Gerald Le Gac, Volkan Okur, Nadege Loaec, Thomas Ludwig, Chandran Ka, Kurenai Tanji, Pascale Marcorelles, Evangelos Theodorou, Angela Lignelli-Dipple, Cecile Voisset, Melissa A. Walker, Lauren C. Briere, Amelie Bourhis, Marc Blondel, Charles LeDuc, Jacob Hagen, Cathleen Cooper, Colleen Muraresku, Claude Ferec, Armelle Garenne, Servane Lelez-Soquet, Cassandra A. Rogers, Yufeng Shen, Dana K. Strode, Peyman Bizargity, Alejandro Iglesias, Amy Goldstein, Frances A. High, David A. Sweetser, Rebecca Ganetzky, Johan L. K. Van Hove, Vincent Procaccio, Cedric Le Marechal, Wendy K. Chung
Summary: Mitochondrial complex V is important for oxidative phosphorylation and a rare variant in ATP5PO gene is associated with a severe multi-systemic disorder consistent with Leigh syndrome.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Pierre Conan, Alice Leon, Mathilde Gourdel, Claire Rollet, Loubna Chair, Noeline Caroff, Nelig Le Goux, Catherine Le Jossic-Corcos, Maha Sinane, Lucile Gentile, Louise Maillebouis, Nadege Loaec, Jennifer Martin, Marie Vilaire, Laurent Corcos, Olivier Mignen, Mikael Croyal, Cecile Voisset, Frederic Bihel, Gaelle Friocourt
Summary: By using a yeast-based screening method, researchers have identified three new potent inhibitors of CBS. They also discovered the importance of copper and zinc levels in regulating the enzymatic activity of CBS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Etienne Auvert, Reidun Aesoy, Francis Giraud, Lars Herfindal, Fabrice Anizon, Pascale Moreau
Summary: By selectively substituting the 1-position, we synthesized a series of new analogues and studied their effects on Pim-1 kinase inhibition and cytotoxicity against AML MOLM-13 cells.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Mathilde Defois, Chloe Remondin, Beatrice Josselin, Lionel Nauton, Vincent Thery, Fabrice Anizon, Sandrine Ruchaud, Francis Giraud, Pascale Moreau
Summary: A new series of pyrazolo[3,4-g]isoquinoline derivatives, diverse in substitution at the 4- or 8-position, were synthesized and evaluated for their kinase inhibitory potency. The results showed that the introduction of a bromine atom at the 8-position had a negative effect on Haspin inhibition, while the introduction of an alkyl group at the 4-position led to a modification of the kinase inhibition profiles. Overall, the new pyrazolo[3,4-g]isoquinolines represent a novel family of kinase inhibitors with various selectivity profiles.
Article
Cell Biology
Tatyana D. Larionova, Soniya Bastola, Tatiana E. Aksinina, Ksenia S. Anufrieva, Jia Wang, Victoria O. Shender, Dmitriy E. Andreev, Tatiana F. Kovalenko, Georgij P. Arapidi, Polina Shnaider, Anastasia N. Kazakova, Yaroslav A. Latyshev, Victor V. Tatarskiy, Alexander A. Shtil, Pascale Moreau, Francis Giraud, Chaoxi Li, Yichan Wang, Maria P. Rubtsova, Olga A. Dontsova, Michael Condro, Benjamin M. Ellingson, Mikhail Shakhparonov, Harley Kornblum, Ichiro Nakano, Marat S. Pavlyukov
Summary: Larionova et al. discover a mechanism by which acidification of the tumour microenvironment induces the generation of an alternative splice isoform of ribosomal protein RPL22L1, which regulates cell stemness and increases tumour heterogeneity. The acidic pH in the tumour core switches the RNA splicing of the ribosomal gene towards the RPL22L1b isoform, allowing cells to survive acidosis and promoting stemness. In the tumour edge region, RPL22L1a interacts with ribosomes and upregulates translation of multiple messenger RNAs including TP53. Targeting this mechanism may decrease GBM heterogeneity and facilitate therapy.
NATURE CELL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Mattias F. Lindberg, Emmanuel Deau, Jonas Arfwedson, Nicolas George, Pascal George, Patricia Alfonso, Ana Corrionero, Laurent Meijer
Summary: This study evaluates the kinase inhibitory activity of a library of DYRKs/CLKs inhibitors and finds a diverse range of potencies and selectivities among these inhibitors, highlighting the challenges of targeting kinases in this area of research. The use of a panel of inhibitors is suggested for studying the functions of these kinases in cellular processes.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Emmanuel Deau, Mattias F. F. Lindberg, Freideiric Miege, Didier Roche, Nicolas George, Pascal George, Andreas Kra''mer, Stefan Knapp, Laurent Meijer
Summary: Dual-specificity,tyrosine phosphorylation-regulated kinases (DYRKs) and cdc2-like kinases (CLKs) have been identified as important targets for various pathologies. In this study, a family of DYRK/CLK inhibitors called Leucettinibs, derived from Leucettines and Leucettamine B, were synthesized and characterized. These inhibitors showed subnanomolar IC50 on DYRK1A and demonstrated potential for therapeutic drug development. Kinase-inactive isomers, iso-Leucettinibs, were also synthesized as suitable negative control compounds. Leucettinibs were found to inhibit DYRK1A substrate phosphorylation in cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Elodie Mauchauffee, Jeremy Leroy, Jihanne Chamcham, Abdelaziz Ejjoummany, Manon Maurel, Lionel Nauton, Booma Ramassamy, Karima Mezghenna, Jean-Luc Boucher, Anne-Dominique Lajoix, Jean-Francois Hernandez
Summary: We developed dipeptidomimetic compounds as potent inhibitors of nNOS and iNOS, showing significant selectivity against eNOS. The extension size was increased to improve interactions in the NOS substrate access channel. Molecular modeling explained the selectivity towards nNOS over eNOS, and spectral studies confirmed interaction at the heme active site. These selected inhibitors were effective in inhibiting intra-cellular nNOS and iNOS in RAW264.7 and INS-1 cells.
Article
Biochemistry & Molecular Biology
Ronan Le Senechal, Marc Keruzore, Alicia Quillevere, Nadege Loaec, Van-Trang Dinh, Oksana Reznichenko, Pedro Guixens-Gallardo, Laurent Corcos, Marie-Paule Teulade-Fichou, Anton Granzhan, Marc Blondel
Summary: BCL-x is a master regulator of apoptosis and its alternative splicing is controlled by RBM25. RBM25 directly binds to an RNA G-quadruplex near the alternative splice site of BCL-x pre-mRNA, promoting the production of the pro-apoptotic Bcl-xS isoform. PhenDC3 and two newly discovered compounds, PhenDH8 and PhenDH9, enhance the binding of RBM25 to the G-quadruplex, thereby promoting apoptosis. This study highlights the importance of the RBM25/G-quadruplex interaction in sensitizing cancer cells to chemotherapy.
NUCLEIC ACIDS RESEARCH
(2023)
Correction
Clinical Neurology
B. Souchet, M. Audrain, Y. Gu, M. F. Lindberg, N. S. Orefice, E. Rey, N. Cartier, N. Janel, L. Meijer, Jerome Braudeau
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2023)
Correction
Geriatrics & Gerontology
B. Souchet, M. Audrain, Y. Gu, M. F. Lindberg, N. S. Orefice, E. Rey, N. Cartier, N. Janel, L. Meijer, Jerome Braudeau
JOURNAL OF NUTRITION HEALTH & AGING
(2022)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
