GLP1R agonists and vorasidenib combine against mutant IDH glioma via peroxynitrite
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A preprint posted on bioRxiv reports that GLP1R agonists and the mutant IDH inhibitor vorasidenib act synergistically against mutant IDH glioma in patient-derived and mouse models. GLP1R agonists drive nitric oxide production through cAMP-PKA signaling, while vorasidenib relieves D-2HG-mediated inhibition of pyruvate dehydrogenase and raises mitochondrial superoxide. Together these effects generate peroxynitrite, which damages lipids and DNA and triggers apoptosis. In mice bearing intracranial mutant IDH tumors, the combination induced tumor regression and significantly prolonged survival. The findings are at the preprint stage and have not yet undergone peer review or clinical testing.
Written by a model from the reports · updated 3 hours ago
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- bioRxivPickGLP1R agonists and vorasidenib converge on peroxynitrite-mediated cytotoxicity in mutant IDH glioma
GLP1R agonists and vorasidenib show synergistic cytotoxicity through the peroxynitrite pathway in patient-derived and mouse models of mutant IDH glioma. Mechanistically, GLP1R agonists induce nitric oxide production via cAMP-PKA signaling, while vorasidenib relieves D-2HG-mediated inhibition of pyruvate dehydrogenase and increases mitochondrial superoxide; the two converge to generate peroxynitrite that damages lipids and DNA and triggers apoptosis. The combination induces tumor regression and significantly prolongs survival in mice bearing intracranial mIDH tumors.
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