ArticleNature chemical biology2022
M24B aminopeptidase inhibitors selectively activate the CARD8 inflammasome.
Article in Nature chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Reverse genetics in humanized mice reveals CARD8-mediated pyroptosis causing pancytopenia in human DPP9 deficiency.The Journal of clinical investigation · 2026Article
- Systematic Targeting of Protein Complexes with Molecular COUPLrs.Cancer discovery · 2026Article
- Reverse genetics in humanized mice reveals CARD8-mediated pyroptosis causing pancytopenia in human DPP9 deficiency.bioRxiv : the preprint server for biology · 2026Article
- An overview of human inflammasomes: Activation and regulation.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- The non-structural protein of SFTSV activates NLRP1 and CARD8 inflammasome through disrupting the DPP9-mediated ternary complex.PLoS pathogens · 2025Article
- Triggering Pyroptosis in Cancer.Biomolecules · 2025Review
- Activation of Inflammasomes and Relevant Modulators for the Treatment of Microglia-mediated Neuroinflammation in Ischemic Stroke.Molecular neurobiology · 2024Review
- Pyroptosis: Induction and inhibition strategies for immunotherapy of diseases.Acta pharmaceutica Sinica. B · 2024Review
- CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity.Cells · 2024Review
- NLRP inflammasomes in health and disease.Molecular biomedicine · 2024Review
- Small molecule modulators of immune pattern recognition receptors.RSC chemical biology · 2023Review
- Article
- Scientific Fluency as the Greatest Strength of Chemical Biologists.Chembiochem : a European journal of chemical biology · 2023Article
- Chemical inhibition of DPP9 sensitizes the CARD8 inflammasome in HIV-1-infected cells.Nature chemical biology · 2023Article
- DPP8/9 are not Required to Cleave Most Proline-Containing Peptides.Israel journal of chemistry · 2023Article
- Optimized M24B Aminopeptidase Inhibitors for CARD8 Inflammasome Activation.Journal of medicinal chemistry · 2023Article
- Protein folding stress potentiates NLRP1 and CARD8 inflammasome activation.Cell reports · 2023Article
- The NLRP1 and CARD8 inflammasomes detect reductive stress.Cell reports · 2023Article
- Race between virus and inflammasomes: inhibition or escape, intervention and therapy.Frontiers in cellular and infection microbiology · 2023Review
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Inflammasomes are multiprotein complexes that sense intracellular danger signals and induce pyroptosis. CARD8 and NLRP1 are related inflammasomes that are repressed by the enzymatic activities and protein structures of the dipeptidyl peptidases 8 and 9 (DPP8/9). Potent DPP8/9 inhibitors such as Val-boroPro (VbP) activate both NLRP1 and CARD8, but chemical probes that selectively activate only one have not been identified. Here we report a small molecule called CQ31 that selectively activates CARD8. CQ31 inhibits the M24B aminopeptidases prolidase (PEPD) and Xaa-Pro aminopeptidase 1 (XPNPEP1), leading to the accumulation of proline-containing peptides that inhibit DPP8/9 and thereby activate CARD8. NLRP1 is distinct from CARD8 in that it directly contacts DPP8/9's active site; these proline-containing peptides, unlike VbP, do not disrupt this repressive interaction and thus do not activate NLRP1. We expect that CQ31 will now become a valuable tool to study CARD8 biology.
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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 OpenQuestion graph.