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Success Stories


Publications
A New Functional Screening Platform Identifies Colistin Sulfate as an Enhancer of Natural Killer Cell Cytotoxicity

Cortés-Kaplan, S.; Kurdieh, R.; Hasim, M. S.; Kaczmarek, S.; Taha, Z.; Maznyi, G.; McComb, S.; Lee, S.-H.; Diallo, J.-S.; Ardolino, M.
Cancers (Basel) 14 (12), 2832 (2022)

Due to their crucial role in tumor immunity, NK cells have quickly became a prime target for immunotherapies, with the adoptive transfer of NK cells and the use of NK cell engagers quickly moving to the clinical stage. On the other hand, only a few studies have focused on small molecule drugs capable of unleashing […]

Publications
A New Topical Candidate in Acne Treatment: Characterization of the Meclozine Hydrochloride as an Anti-Inflammatory Compound from In Vitro to a Preliminary Clinical Study

Grange, P. A.; Ollagnier, G.; Beauvais Remigereau, L.; Nicco, C.; Mayslich, C.; Marcelin, A.-G.; Calvez, V.; Dupin, N.
Biomedicines 10 (5), 931 (2022)

Acne is a chronic inflammatory multifactorial disease involving the anaerobic bacterium Cutibacterium acnes (C. acnes). Current acne treatments are associated with adverse effects, limiting treatment compliance and use. We showed that meclozine, an anti-histaminic H1 compound, has anti-inflammatory properties. In Vitro, meclozine reduced the production of CXCL8/IL-8 and IL-1β mRNA and protein by C. acnes-stimulated […]

Publications
Identification of Drug Transporter Genomic Variants and Inhibitors That Protect Against Doxorubicin-Induced Cardiotoxicity

Magdy, T.; Jouni, M.; Kuo, H.-H.; Weddle, C. J.; Lyra-Leite, D.; Fonoudi, H.; Romero-Tejeda, M.; Gharib, M.; Javed, H.; Fajardo, G.; Ross, C. J. D.; Carleton, B. C.; Bernstein, D.; Burridge, P. W.
Circulation 145 (4), 279–294 (2022)

BACKGROUND: Multiple pharmacogenomic studies have identified the synonymous genomic variant rs7853758 (G > A, L461L) and the intronic variant rs885004 in SLC28A3 (solute carrier family 28 member 3) as statistically associated with a lower incidence of anthracycline-induced cardiotoxicity. However, the true causal variant(s), the cardioprotective mechanism of this locus, the role of SLC28A3 and other […]

Publications
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 […]

Publications
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 […]

Publications
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 […]

Publications
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 […]

Publications
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 […]

Publications
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 […]

Publications
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 […]