DMB | Gasdermin D agonist/GLP-1 agonist

DMB chemical structure

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DMB (281209-71-0) is a small molecule glucagon-like peptide 1 (GLP-1) ago-allosteric modulator and agonist (EC50 = 101 nM).1 It significantly stimulated insulin secretion in BRIN-BD11 cells and decreased overall glucose excursion in mice.2  DMB is a direct and selective gasdermin D (GSDMD) agonist that activates GSDMD pore formation and pyroptosis without cleaving GSDMD (EC50 = 700 nM).3 It induced pyroptosis in mouse cancer cell lines and induced tumor regression and enhanced antitumor immunity.  DMB-treated tumor cells acted as a tumor vaccine in mice indicating that DMB can trigger immunogenic cell death that provides protective antitumor immunity.

References/Citations:

  1. Knudsen et al. (2007), Small-molecule agonists for the glucagon-like peptide 1 receptor; Proc. Natl. Acad. Sci. USA 104 937
  2. Irwin et al. (2010), Insulin-releasing and metabolic effects of small molecule GLP-1 receptor agonist 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline; Eur. J. Pharmacol. 628 268
  3. Fontana et al. (2024), Small-molecule GSDMD agonism in tumors stimulates antitumor immunity without toxicity; Cell 187 6165
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DMB (281209-71-0) is a small molecule glucagon-like peptide 1 (GLP-1) ago-allosteric modulator and agonist (EC50 = 101 nM).1 It significantly stimulated insulin secretion in BRIN-BD11 cells and decreased overall glucose excursion in mice.2  DMB is a direct and selective gasdermin D (GSDMD) agonist that activates GSDMD pore formation and pyroptosis without cleaving GSDMD (EC50 = 700 nM).3 It induced pyroptosis in mouse cancer cell lines and induced tumor regression and enhanced antitumor immunity.  DMB-treated tumor cells acted as a tumor vaccine in mice indicating that DMB can trigger immunogenic cell death that provides protective antitumor immunity.

References/Citations:

  1. Knudsen et al. (2007), Small-molecule agonists for the glucagon-like peptide 1 receptor; Proc. Natl. Acad. Sci. USA 104 937
  2. Irwin et al. (2010), Insulin-releasing and metabolic effects of small molecule GLP-1 receptor agonist 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline; Eur. J. Pharmacol. 628 268
  3. Fontana et al. (2024), Small-molecule GSDMD agonism in tumors stimulates antitumor immunity without toxicity; Cell 187 6165