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 […]

A fluorescence-based high throughput-screening assay for the SARS-CoV RNA synthesis complex

Journal of Virological Methods

Eydoux C, Fattorini V, Shannon A, Le TTN, Didier B, Canard B, Guillemot JC
Journal of Virological Methods - vol. 288 114013 (2021)

The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) emergence in 2003 introduced the first serious human coronavirus pathogen to an unprepared world. To control emerging viruses, existing successful anti(retro)viral therapies can inspire antiviral strategies, as conserved viral enzymes (eg., viral proteases and RNA-dependent RNA polymerases) represent targets of choice. Since 2003, much effort has been expended […]

High content drug screening for Fanconi anemia therapeutics

Orphanet Journal of Rare Diseases

Montanuy H, Camps-Fajol C, Camps-Fajol C, Carreras-Puigvert J, Carreras-Puigvert J, Carreras-Puigvert J, Häggblad M, Häggblad M, Lundgren B, Aza-Carmona M, Aza-Carmona M, Helleday T, Minguillón J, Minguillón J, Minguillón J, Surrallés J, Surrallés J, Surrallés J, Surrallés J
Orphanet Journal of Rare Diseases - vol. 15 1-9 (2020)

Background: Fanconi anemia is a rare disease clinically characterized by malformations, bone marrow failure and an increased risk of solid tumors and hematologic malignancies. The only therapies available are hematopoietic stem cell transplantation for bone marrow failure or leukemia, and surgical resection for solid tumors. Therefore, there is still an urgent need for new therapeutic […]

Drosophila SMN2 minigene reporter model identifies moxifloxacin as a candidate therapy for SMA

FASEB Journal

Konieczny P, Artero R
FASEB Journal - vol. 34 3021-3036 (2020)

Spinal muscular atrophy is a rare and fatal neuromuscular disorder caused by the loss of alpha motor neurons. The affected individuals have mutated the ubiquitously expressed SMN1 gene resulting in the loss or reduction in the survival motor neuron (SMN) protein levels. However, an almost identical paralog exists in humans: SMN2. Pharmacological activation of SMN2 […]