A high-throughput screening assay for small molecule inhibitors of the antigen aminopeptidase ERAP1

The January 2023 issue of SLAS Discovery contains a collection of four full-length articles and one technical brief covering cancer research, high-throughput screening (HTS) assay development and other drug discovery exploration.

This month’s featured article, “A high-throughput MALDI-TOF MS biochemical screen for small molecule inhibitors of the antigen aminopeptidase ERAP1,” by Müller, et al, presents a newly developed matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) drug discovery assay for the endoplasmic reticulum aminopeptidase 1 (ERAP1). The dysregulation of ERAP1 has been associated with various auto-immune and auto-inflammatory diseases, making ERAP1 a high-profile target in drug discovery.

The research team behind this study utilized an existing ERAP1 RapidFire MS (RF MS) assay on which to base their MALDI-TOF assay, producing greater assay stability, reproducibility and robustness for the MALDI-TOF platform. When results were compared between the pre-established RF MS and the MALDI-TOF platforms, shorter sample cycle times, reduced reagent consumption and a lower tight-binding limit were all advantages of the MALDI-TOF platform.

Read this original research article to learn how the MALDI-TOF platform may detect other difficult targets, along with more research articles in the January issue of SLAS Discovery.

The January issue of SLAS Discovery includes these additional articles:

• The SLAS Discovery Editor’s Top 10 for 2022
• Reduced levels of serum EPA and DHA identified in patients with non-small-cell lung cancer using a new rapid validated LC-MS/MS method
• DNA methylation-induced ablation of miR-133a accelerates cancer aggressiveness in glioma through upregulating peroxisome proliferator-activated receptor γ
• Optimising cell-based bioassays via integrated design of experiments (ixDoE) – A practical guide
• Development of a high-throughput TR-FRET screening assay for a fast-cycling KRAS mutant
• Corrigendum to DNA methylation-induced ablation of miR-133a accelerates cancer aggressiveness in glioma through upregulating peroxisome proliferator-activated receptor γ [SLAS Discov. 2022 Sep 5;S2472-5552(22)13691-9. doi: 10.1016/j.slasd.2022.08.004.]