Development of a Cell-Based AlphaLISA Assay for High-Throughput Screening for Small Molecule Proteasome Modulators

The balance between protein degradation and protein synthesis is a highly choreographed process generally called proteostasis

Sophia D Staerz, Erika M Lisabeth, Evert Njomen, Thomas S Dexheimer, Richard R Neubig , Jetze J Tepe
ACS Omega 15650-15659 (2023)

Most intracellular protein degradation occurs through the ubiquitin-proteasome system (UPS). This degradation takes place through either a ubiquitin-dependent or a ubiquitin-independent proteasomal pathway. The ubiquitin-independent pathway selectively targets unfolded proteins, including intrinsically disordered proteins (IDPs). Dysregulation of proteolysis can lead to the accumulation of IDPs, seen in the pathogenesis of various diseases, including cancer and […]

Drug Repositioning as a Therapeutic Strategy against Streptococcus pneumoniae: Cell Membrane as Potential Target

Laura Ortiz-Miravalles, Manuel Sánchez-Angulo, Jesús M Sanz , Beatriz Maestro
Int. J. Mol. Sci. 5831 (2023)

A collection of repurposing drugs (Prestwick Chemical Library) containing 1200 compounds was screened to investigate the drugs’ antimicrobial effects against planktonic cultures of the respiratory pathogen Streptococcus pneumoniae. After four discrimination rounds, a set of seven compounds was finally selected, namely (i) clofilium tosylate; (ii) vanoxerine; (iii) mitoxantrone dihydrochloride; (iv) amiodarone hydrochloride; (v) tamoxifen citrate; […]

PAX8 Modulates the Tumor Microenvironment of High Grade Serous Ovarian Cancer through Changes in the Secretome

Salvi, A.; Hardy, L. R.; Heath, K. N.; Watry, S.; Pergande, M. R.; Cologna, S. M.; Burdette, J. E.
Neoplasia 36, 100866 (2023)

High grade serous ovarian cancer (HGSC) arises from the fimbriated end of the fallopian tube epithelium (FTE), and in some cases, the ovarian surface epithelium (OSE). PAX8 is a commonly used biomarker for HGSC and is expressed in ∼90% of HGSC. Although the OSE does not express PAX8, murine models of HGSC derived from the […]

Novel Non-Stimulants Rescue Hyperactive Phenotype in an Adgrl3.1 Mutant Zebrafish Model of ADHD

Sveinsdóttir, H. S.; Christensen, C.; Þorsteinsson, H.; Lavalou, P.; Parker, M. O.; Shkumatava, A.; Norton, W. H. J.; Andriambeloson, E.; Wagner, S.; Karlsson, K. Æ
Neuropsychopharmacology (2022)

ADHD is a highly prevalent neurodevelopmental disorder. The first-line therapeutic for ADHD, methylphenidate, can cause serious side effects including weight loss, insomnia, and hypertension. Therefore, the development of non-stimulant-based therapeutics has been prioritized. However, many of these also cause other effects, most notably somnolence. Here, we have used a uniquely powerful genetic model and unbiased […]

Drug Screening Approach against Mycobacterial Fatty Acyl-AMP Ligase FAAL32 Renews the Interest of the Salicylanilide Pharmacophore in the Fight against Tuberculosis

Le, N.-H.; Constant, P.; Tranier, S.; Nahoum, V.; Guillet, V.; Maveyraud, L.; Daffé, M.; Mourey, L.; Verhaeghe, P.; Marrakchi, H.
Bioorg Med Chem 71, 116938 (2022)

Tuberculosis (TB) remains a global health crisis, further exacerbated by the slow pace of new treatment options, and the emergence of extreme and total drug resistance to existing drugs. The challenge to developing new antibacterial compounds with activity against Mycobacterium tuberculosis (Mtb), the causative agent of TB, is in part due to unique features of […]

A New Use for Old Drugs: Identifying Compounds with an Anti-Obesity Effect Using a High through-Put Semi-Automated Caenorhabditis Elegans Screening Platform

Haerkens, F.; Kikken, C.; Kirkels, L.; van Amstel, M.; Wouters, W.; van Doornmalen, E.; Francke, C.; Hughes, S.
Heliyon 8 (8), e10108 (2022)

Obesity is one of the most common global health problems for all age groups with obese people at risk of a variety of associated health complications. Consequently, there is a need to develop new therapies that lower body fat without the side effects. However, obesity is a complex and systemic disease, so that in vitro […]

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 […]

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 […]

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 […]

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 […]