ArticleNature chemical biology2017
DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis.
Article in Nature chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 177 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
177 citing papers in PubMed, 302 citations in OpenAlex.
- Phase 2 study of talabostat, a small molecule inhibitor of dipeptidyl peptidases (DPP), administered in combination with pembrolizumab in patients with small cell neuroendocrine prostate cancer.Journal for immunotherapy of cancer · 2026Trial
- Trial
- Reverse genetics in humanized mice reveals CARD8-mediated pyroptosis causing pancytopenia in human DPP9 deficiency.The Journal of clinical investigation · 2026Article
- IFN-α and IFN-β inhibit NLRP1-driven PANoptosis.EMBO reports · 2026Article
- Integrated Cytokine, Metabolic, and Proliferative Profiling Reveals Divergent Metabolic and Proliferative Responses in Papillary Thyroid Cancer Cells.International journal of molecular sciences · 2026Article
- DPP9-mediated inflammasome repression protects against checkpoint inhibitor lung toxicity.bioRxiv : the preprint server for biology · 2026Article
- Reverse genetics in humanized mice reveals CARD8-mediated pyroptosis causing pancytopenia in human DPP9 deficiency.bioRxiv : the preprint server for biology · 2026Article
- Disease-associated genetic variants can cause missense effects in tissue-specific protein isoforms.Nature communications · 2026Article
- Article
- MST1 promotes microglial pyroptosis and neuroinflammation in alzheimer's disease by regulating the novel DPP8/NLRP1/Caspase-1/GSDMD-N axis.Journal of neuroinflammation · 2026Article
- Prostate Cancer-Associated Fibroblasts: A Review on CAF Functions, Heterogeneity, Resistance Mechanisms, and Future in a Chip.International journal of molecular sciences · 2026Review
- Proximity labeling reveals non-catalytic interactions between DPP9 and ubiquitin signaling complexes.Cellular and molecular life sciences : CMLS · 2026Article
- Methylglyoxal-modification of NLRP3 interrupts NLRP3-NEK7 interaction diminishing inflammasome activation and neuroinflammation.Journal of neuroinflammation · 2026Article
- Supramolecular Assemblies Drive Activation of Inflammasomes.Advances in experimental medicine and biology · 2026Review
- Methylation of DPP9 regulates immune surveillance in non-small cell lung cancer by promoting macrophage ferroptosis via WWP2 ubiquitination.American journal of cancer research · 2026Article
- Tegavivint triggers TECR-dependent nonapoptotic cancer cell death.Nature chemical biology · 2025Article
- Pyroptosis of Vascular Smooth Muscle Cells as a Potential New Target for Preventing Vascular Diseases.Cardiovascular drugs and therapy · 2025Review
- Article
- Human non-canonical inflammasomes activate CASP3 to limit intracellularbioRxiv : the preprint server for biology · 2025Article
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
117 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
Val-boroPro (Talabostat, PT-100), a nonselective inhibitor of post-proline cleaving serine proteases, stimulates mammalian immune systems through an unknown mechanism of action. Despite this lack of mechanistic understanding, Val-boroPro has attracted substantial interest as a potential anticancer agent, reaching phase 3 trials in humans. Here we show that Val-boroPro stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. We demonstrate that the inhibition of two serine proteases, DPP8 and DPP9, activates the pro-protein form of caspase-1 independent of the inflammasome adaptor ASC. Activated pro-caspase-1 does not efficiently process itself or IL-1β but does cleave and activate gasdermin D to induce pyroptosis. Mice lacking caspase-1 do not show immune stimulation after treatment with Val-boroPro. Our data identify what is to our knowledge the first small molecule that induces pyroptosis and reveals a new checkpoint that controls the activation of the innate immune system.
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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.