title: Drug Signature-based Finding of Additional Clinical Use of LC28-0126 for Neutrophilic Bronchial Asthma.
abstract: In recent decades, global pharmaceutical companies have suffered from an R&D innovation gap between the increased cost of a new drug's development and the decreased number of approvals. Drug repositioning offers another opportunity to fill the gap because the approved drugs have a known safety profile for human use, allowing for a reduction of the overall cost of drug development by eliminating rigorous safety assessment. In this study, we compared the transcriptional profile of LC28-0126, an investigational drug for acute myocardial infarction (MI) at clinical trial, obtained from healthy male subjects with molecular activity profiles in the Connectivity Map. We identified dyphilline, an FDA-approved drug for bronchial asthma, as a top ranked connection with LC28-0126. Subsequently, we demonstrated that LC28-0126 effectively ameliorates the pathophysiology of neutrophilic bronchial asthma in OVALPS-OVA mice accompanied with a reduction of inflammatory cell counts in the bronchoalveolar lavage fluid (BALF), inhibition of the release of proinflammatory cytokines, relief of airway hyperactivity, and improvement of histopathological changes in the lung. Taken together, we suggest that LC28-0126 could be a potential therapeutic for bronchial asthma. In addition, this study demonstrated the potential general utility of computational drug repositioning using clinical profiles of the investigational drug.
authors.affiliation: LG Life Sciences R&D Park, Daejeon, 305-380, Republic of Korea.
authors.forename: Eunji
authors.initials: E
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine, Research Center for Pulmonary Disorder, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, 561-180, Republic of Korea.
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Research Center for Pulmonary Disorder, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, 561-180, Republic of Korea.
authors.forename: So Ri
authors.initials: SR
authors.lastname: Kim
authors.affiliation: LG Life Sciences R&D Park, Daejeon, 305-380, Republic of Korea.
authors.forename: Soon Ha
authors.initials: SH
authors.lastname: Kim
authors.affiliation: LG Life Sciences R&D Park, Daejeon, 305-380, Republic of Korea.
authors.forename: Joonghoon
authors.initials: J
authors.lastname: Park
mesh_terms: D000328:Adult; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged
chemical_list: D018927:Anti-Asthmatic Agents; D016207:Cytokines