Effectiveness and mechanistic effects of green mamba peptide MQ232 in an orthologous mouse model of Autosomal Dominant Polycystic Kidney Disease - PubMed
3 hours ago
- #ADPKD
- #peptide therapy
- #V2 receptor
- MQ232, a green mamba-derived peptide and V2R inverse agonist, was tested in Pkd1RC/RC mice as a potential treatment for ADPKD.
- MQ232 and tolvaptan equally attenuated polycystic kidney disease in mice, despite dose-dependent differences in cAMP reduction and urine output.
- High doses of MQ232 and tolvaptan may activate cAMP-independent pathways (e.g., Src, ERK), potentially limiting therapeutic benefits.
- Both compounds downregulated PAPPA, but MQ232 uniquely inhibited IGF1Rβ phosphorylation compared to tolvaptan.
- The study suggests that titrating V2R inverse agonists to maximally tolerated doses may not be optimal due to activation of alternative cystogenic pathways.