ArticleAngewandte Chemie (International ed. in English)2022
Discovery of the First Selective Nanomolar Inhibitors of ERAP2 by Kinetic Target-Guided Synthesis.
Article in Angewandte Chemie (International ed. in English), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Review
- Click Reactions in Kinetic Target-Guided Synthesis: Progress in the Discovery of Inhibitors for Biological Targets.Methods and protocols · 2026Review
- Methods and Guidelines for Analyzing the Conformational Dynamics of Proteins in the Antigen Presentation Pathway.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Utilising genomic association data for causal inference in anorexia nervosa.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Discovery of Boronic Acids-Based β-Lactamase Inhibitors Through In Situ Click Chemistry.International journal of molecular sciences · 2025Article
- Discovery of New Nanomolar Selective IRAP Inhibitors.Journal of medicinal chemistry · 2025Article
- Unveiling the impact of ERAP1 and ERAP2 on migration, angiogenesis and ER stress response.Frontiers in cell and developmental biology · 2025Review
- Transcriptome-wide Mendelian randomization during CD4Nature communications · 2024Article
- ERAP Inhibitors in Autoimmunity and Immuno-Oncology: Medicinal Chemistry Insights.Journal of medicinal chemistry · 2024Review
- Biology of HLA class I associated inflammatory diseases.Best practice & research. Clinical rheumatology · 2024Review
- Shotgun Kinetic Target-Guided Synthesis Approach Enables the Discovery of Small-Molecule Inhibitors against Pathogenic Free-Living Amoeba Glucokinases.ACS infectious diseases · 2023Article
- Going beyond Binary: Rapid Identification of Protein-Protein Interaction Modulators Using a Multifragment Kinetic Target-Guided Synthesis Approach.Journal of medicinal chemistry · 2023Article
- Discovery of the First Selective Nanomolar Inhibitors of ERAP2 by Kinetic Target-Guided Synthesis.Angewandte Chemie (International ed. in English) · 2022Article
Corrections and comments
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Authors and funding
29 authors at 5 institutions in 4 countries.
Funding
Abstract
Endoplasmic reticulum aminopeptidase 2 (ERAP2) is a key enzyme involved in the trimming of antigenic peptides presented by Major Histocompatibility Complex class I. It is a target of growing interest for the treatment of autoimmune diseases and in cancer immunotherapy. However, the discovery of potent and selective ERAP2 inhibitors is highly challenging. Herein, we have used kinetic target-guided synthesis (KTGS) to identify such inhibitors. Co-crystallization experiments revealed the binding mode of three different inhibitors with increasing potency and selectivity over related enzymes. Selected analogues engage ERAP2 in cells and inhibit antigen presentation in a cellular context. 4 d (BDM88951) displays favorable in vitro ADME properties and in vivo exposure. In summary, KTGS allowed the discovery of the first nanomolar and selective highly promising ERAP2 inhibitors that pave the way of the exploration of the biological roles of this enzyme and provide lead compounds for drug discovery efforts.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.