In cystic fibrosis (CF), cAMP-mediated Cl- transport in secretory epithelia is defective, leaving chloride secretion via the calcium dependent Cl- pathways at least partially intact and the latter is therefore a focal point for potential therapeutic use. Compounds that influence the calcium-activated Cl- secretion are currently developed by SiChem. Recent results show that the lead compound, a membrane-permeant derivative of an intracellular messenger molecule, is able to increase Cl- secretion in epithelia from cystic fibrosis patients. Since the compounds are directed towards targets deep down in the signaling cascade little no side effects are expected. This success may be considered proof of concept regarding the feasibility of our platform.
SiChem synthesized for ISM Therapeutics (Seattle, USA) INO-4995, an IP4 analogue with clinical potential in CF through ascertaining in vivo activity in mice with CF
Other derivatives designed following the same concept are powerful inhibitors of epithelial chloride secretion and are therefore considered lead compounds against diarrhea, the most widespread lethal disease on earth. Other co-developments are pursued to generate anti-inflammatory drugs.