Inhaled sGC stimulator frespaciguat designed for lung-selective action in PH-COPD
- Oral sGC stimulators can lower systemic blood pressure and worsen ventilation-perfusion matching in COPD-related pulmonary hypertension, so an inhaled, property-driven design was pursued.
- SAR and pharmacokinetic work showed that fast systemic clearance plus low permeability drives lung selectivity.
- Frespaciguat (MK-5475) is very potent with long target residence and lung-biased exposure; in rats it lowered pulmonary arterial pressure dose-dependently, with little systemic effect, for over a day.
💡 Points Based on the abstract
Designing for low permeability plus high systemic clearance runs against what we usually chase in an sGC stimulator, and it is a clean way to buy lung selectivity without a gated delivery trick. The worry is how much lung retention depends on formulation and particle deposition rather than the molecule. Long target residence time is what should make once-daily dosing plausible.