Identification of Drug Candidates to Suppress Cigarette Smoke-induced Inflammation via cMap Analyses

Cigarette smoking is the main risk factor for chronic obstructive pulmonary disease, and to date, existing pharmacologic interventions have been ineffective at controlling inflammatory processes associated with the disease. To address this issue, we used the Connectivity Map (cMap) database to identify drug candidates with the potential to attenuate cigarette smoke–induced inflammation. We queried cMap using three independent in-house cohorts of healthy nonsmokers and smokers. Potential drug candidates were validated against four publicly available human datasets, as well as six independent datasets from cigarette smoke–exposed mice. Overall, these analyses yielded two potential drug candidates: kaempferol and bethanechol. Subsequently, the efficacy of each drug was validated in vivo in a model of cigarette smoke–induced inflammation. BALB/c mice were exposed to room air or cigarette smoke and treated with each of the two candidate drugs either prophylactically or therapeutically. We found that kaempferol...