Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications
Pharmacology and pharmaceutical sciences
610 Medical sciences Medicine
RA1190-1270
Toxicology. Poisons
610
Therapeutics. Pharmacology
RM1-950
320
Other chemical sciences
Meeting Abstracts
DOI:
10.1186/s40360-017-0170-5
Publication Date:
2017-10-10T08:54:15Z
AUTHORS (480)
ABSTRACT
The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signalling pathway plays a fundamental role in modulating diverse physiological processes including blood flow, fibrosis, inflammation, and metabolism.sGC stimulators are small-molecule, heme-dependent agonists of sGC that synergize with enhance endogenous NO signaling.As such, may provide therapeutic benefits both diseases associated impaired signaling where stimulation this will restore functional homeostasis.Data from our recent preclinical studies add to the growing body evidence have direct effects on systemic vascular metabolism.Ironwood is developing IW-1973 IW-1701 as oral, once-daily for cardiovascular non-cardiovascular disease indications.Phase 1 healthy human subjects demonstrated clear target engagement, attractive pharmacokinetic properties, predicted hemodynamic effects, at well-tolerated doses.Phase 2 currently ongoing patients achalasia, an esophageal motility disorder, diabetes hypertension.Preclinical characterization support broad potential multi-faceted pharmacology these compounds.Based studies, has extensive distribution into organs liver, heart, kidney, lung, which maximize while limiting effects.The profile narrow peak-to-trough ratio, more consistent pharmacological effect throughout dosing interval.Ironwood also IW-6463, novel, CNS-penetrant stimulator shows engagement regional flow brain.Preclinical data suggest IW-6463 be useful treating CNS disorders dementia Alzheimer's disease.We believe stimulation, alone or combination other mechanisms, afford benefit multiple diseases.Furthermore, there opportunity targeted treatments by selecting compounds well-suited specific based profile, tissue distribution, pharmacokinetics, route administration.Competing interest
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (0)
CITATIONS (0)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....