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Success Stories


Publications
GSK3 Inhibition Reduces ECM Production and Prevents Age-Related Macular Degeneration-like Pathology

Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy (ML/DHRD) is an age-related macular degeneration (AMD)-like retinal dystrophy caused by an autosomal dominant R345W mutation in the secreted glycoprotein, fibulin-3 (F3)

DiCesare, S. M.; Ortega, A. J.; Collier, G. E.; Daniel, S.; Thompson, K. N.; McCoy, M. K.; Posner, B. A.; Hulleman, J. D.
bioRxiv December 15 p 2023.12.14.571757 (2023)

To identify new small molecules that reduce F3 production from retinal pigmented epithelium (RPE) cells, we knocked-in a luminescent peptide tag (HiBiT) into the endogenous F3 locus which enabled simple, sensitive, and high throughput detection of the protein. The GSK3 inhibitor, CHIR99021 (CHIR), significantly reduced F3 burden (expression, secretion, and intracellular levels) in immortalized RPE […]

Publications
Metixene Is an Incomplete Autophagy Inducer in Preclinical Models of Metastatic Cancer and Brain Metastases

A paucity of chemotherapeutic options for metastatic brain cancer limits patient survival and portends poor clinical outcomes.

Fares, J.; Petrosyan, E.; Kanojia, D.; Dmello, C.; Cordero, A.; Duffy, J. T.; Yeeravalli, R.; Sahani, M. H.; Zhang, P.; Rashidi, A.; Arrieta, V. A.; Ulasov, I.; Ahmed, A. U.; Miska, J.; Balyasnikova, I. V.; James, C. D.; Sonabend, A. M.; Heimberger, A. B.; Lesniak, M. S
J Clin Invest e161142 (2023)

Using a CNS small-molecule inhibitor library of 320 agents known to be blood-brain barrier permeable and approved by the FDA, we interrogated breast cancer brain metastasis vulnerabilities to identify an effective agent. Metixene, an antiparkinsonian drug, was identified as a top therapeutic agent that was capable of decreasing cellular viability and inducing cell death across […]

Publications
Identification of small molecule inhibitors against MMP-14 via High-Throughput screening

Matrix metalloproteinases (MMPs) are involved in various cellular events in physiology and pathophysiology through endopeptidases activity.

Hyun Lee, Isoo Youn, Robel Demissie, Tasneem M Vaid, Chun-Tao Che, Dimitri T Azar, Kyu-Yeon Han
Bioorg Med Chem Volume 85, 1 May 2023, 117289 (2023)

The expression levels and activities of most MMPs remain minimal in the normal conditions, whereas some MMPs are significantly activated in pathological conditions such as cancer and neovascularization. Hence, MMPs are considered as both diagnostic markers and potential targets for therapeutic agents. Twenty-three known human MMPs share a similar active site structure with a zinc-binding […]

Publications
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 […]

Case studies
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; […]

Publications
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; […]

Publications
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 […]

Publications
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 […]

Publications
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 […]

Publications
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 […]