High-Throughput Cell-Based Assays for Identifying Antagonists of Multiple Smoking-Associated Human Nicotinic Acetylcholine Receptor Subtypes

Kassner, M.; Eaton, J. B.; Tang, N.; Petit, J. L.; Meurice, N.; Yin, H. H.; Whiteaker, P.
SLAS Discovery 27 (1), 68–76 (2022)

There is substantial evidence that in addition to nicotine, other compounds found in tobacco smoke significantly influence smoking behavior. Further, recent years have seen an explosion in the availability of non-combusted products that deliver nicotine, such as e-cigarettes and “home-brew” vaping devices that are essentially unregulated. There are many thousands of compounds in tobacco smoke […]

A High-Throughput Chemical Screen in DJ-1β Mutant Flies Identifies Zaprinast as a Potential Parkinson’s Disease Treatment

Sanz, F. J.; Solana-Manrique, C.; Torres, J.; Masiá, E.; Vicent, M. J.; Paricio, N.
Neurotherapeutics 18 (4), 2565–2578 (2021)

Dopamine replacement represents the standard therapy for Parkinson’s disease (PD), a common, chronic, and incurable neurological disorder; however, this approach only treats the symptoms of this devastating disease. In the search for novel disease-modifying therapies that target other relevant molecular and cellular mechanisms, Drosophila has emerged as a valuable tool to study neurodegenerative diseases due […]

Sanguinarine Inhibits the 2-Ketogluconate Pathway of Glucose Utilization in Pseudomonas Aeruginosa

Falchi, F. A.; Borlotti, G.; Ferretti, F.; Pellegrino, G.; Raneri, M.; Schiavoni, M.; Caselli, A.; Briani, F.
Front Microbiol 12, 744458 (2021)

Interfering with the ability of pathogenic bacteria to import glucose may represent a new promising antibacterial strategy, especially for the treatment of infections occurring in diabetic and other hyperglycemic patients. Such patients are particularly susceptible to infections caused by a variety of bacteria, among which opportunistic pathogens like Pseudomonas aeruginosa. In P. aeruginosa, glucose can […]

High-Throughput Screening of TRPV1 Ligands in the Light of the Bioluminescence Resonance Energy Transfer Technique

Chappe, Y.; Michel, P.; Joushomme, A.; Barbeau, S.; Pierredon, S.; Baron, L.; Garenne, A.; Gannes, F. P. D.; Hurtier, A.; Mayer, S.; Lagroye, I.; Quignard, J.-F.; Ducret, T.; Compan, V.; Franchet, C.; Percherancier, Y.
Mol Pharmacol 100 (3), 237–257 (2021)

Ion channels are attractive drug targets for many therapeutic applications. However, high-throughput screening (HTS) of drug candidates is difficult and remains very expensive. We thus assessed the suitability of the bioluminescence resonance energy transfer (BRET) technique as a new HTS method for ionchannel studies by taking advantage of our recently characterized intra- and intermolecular BRET […]

Isoconazole and Clemizole Hydrochloride Partially Reverse the Xeroderma Pigmentosum C Phenotype

Kobaisi, F.; Sulpice, E.; Barette, C.; Fayyad, N.; Fauvarque, M.-O.; Badran, B.; Fayyad-Kazan, M.; Fayyad-Kazan, H.; Gidrol, X.; Rachidi, W.
Int J Mol Sci 22 (15) (2021)

Xeroderma Pigmentosum protein C (XPC) is involved in recognition and repair of bulky DNA damage such as lesions induced by Ultra Violet (UV) radiation. XPC-mutated cells are, therefore, photosensitive and accumulate UVB-induced pyrimidine dimers leading to increased cancer incidence. Here, we performed a high-throughput screen to identify chemicals capable of normalizing the XP-C phenotype (hyper-photosensitivity […]

Identification of Harmine and β-Carboline Analogs from a High-Throughput Screen of an Approved Drug Collection; Profiling as Differential Inhibitors of DYRK1A and Monoamine Oxidase A and for in Vitro and in Vivo Anti-Cancer Studies

Tarpley, M.; Oladapo, H. O.; Strepay, D.; Caligan, T. B.; Chdid, L.; Shehata, H.; Roques, J. R.; Thomas, R.; Laudeman, C. P.; Onyenwoke, R. U.; Darr, D. B.; Williams, K. P.
European Journal of Pharmaceutical Sciences 162, 105821 (2021)

DYRK1A (dual-specificity tyrosine phosphorylation-regulated kinase 1a) is highly expressed in glioma, an aggressive brain tumor, and has been proposed as a therapeutic target for cancer. In the current study, we have used an optimized and validated time-resolved fluorescence energy transfer (TR-FRET)-based DYRK1A assay for high-throughput screening (HTS) in 384-well format. A small-scale screen of the […]

Inhibition of Iduronic Acid Biosynthesis by Ebselen Reduces Glycosaminoglycan Accumulation in Mucopolysaccharidosis Type I Fibroblasts

Maccarana, M.; Tykesson, E.; Pera, E. M.; Gouignard, N.; Fang, J.; Malmström, A.; Ghiselli, G.; Li, J.
Glycobiology 31 (10), 1319–1329 (2021)

Mucopolysaccharidosis type I (MPS-I) is a rare lysosomal storage disorder caused by deficiency of the enzyme alpha-L-iduronidase, which removes iduronic acid in both chondroitin/dermatan sulfate (CS/DS) and heparan sulfate (HS) and thereby contributes to the catabolism of glycosaminoglycans (GAGs). To ameliorate this genetic defect, the patients are currently treated by enzyme replacement and bone marrow […]

Identification of Novel Myelin Repair Drugs by Modulation of Oligodendroglial Differentiation Competence

Manousi, A.; Göttle, P.; Reiche, L.; Cui, Q.-L.; Healy, L. M.; Akkermann, R.; Gruchot, J.; Schira-Heinen, J.; Antel, J. P.; Hartung, H.-P.; Küry, P.
EBioMedicine 65, 103276 (2021)

Background: In multiple sclerosis loss of myelin and oligodendrocytes impairs saltatory signal transduction and leads to neuronal loss and functional deficits. Limited capacity of oligodendroglial precursor cells to differentiate into mature cells is the main reason for inefficient myelin repair in the central nervous system. Drug repurposing constitutes a powerful approach for identification of pharmacological […]

Identification of Lysosome‐targeting Drugs with Anti‐inflammatory Activity as Potential Invasion Inhibitors of Treatment Resistant HER2 Positive Cancers

Hansen, M. B.; Postol, M.; Tvingsholm, S.; Nielsen, I. Ø.; Dietrich, T. N.; Puustinen, P.; Maeda, K.; Dinant, C.; Strauss, R.; Egan, D.; Jäättelä, M.; Kallunki, T.
Cell Oncol (Dordr) 44 (4) 805–820 (2019)

Purpose: Most HER2 positive invasive cancers are either intrinsic non-responsive or develop resistance when treated with 1st line HER2 targeting drugs. Both 1st and 2nd line treatments of HER2 positive cancers are aimed at targeting the HER2 receptor directly, thereby strongly limiting the treatment options of HER2/ErbB2 inhibition resistant invasive cancers. Methods: We used phenotypic […]

Exploring the Human Cytomegalovirus Core Nuclear Egress Complex as a Novel Antiviral Target: A New Type of Small Molecule Inhibitors

Alkhashrom S, Kicuntod J, Häge S, Schweininger J, Muller YA, Lischka P, Marschall M, Eichler J.
Viruses 471 (2021)

Nuclear egress is an essential process in the replication of human cytomegalovirus (HCMV), as it enables the migration of newly formed viral capsids from the nucleus into the cytoplasm. Inhibition of the HCMV core nuclear egress complex (core NEC), composed of viral proteins pUL50 and pUL53, has been proposed as a potential new target for […]