{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T03:26:17Z","timestamp":1793935577146,"version":"4.8.0"},"reference-count":28,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Johnson & Johnson Innovative Medicine"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Aerosol Medicine and Pulmonary Drug Delivery"],"published-print":{"date-parts":[[2026,12,1]]},"abstract":"\n Background:<\/jats:title>\n Inhalation of corticosteroids, bronchodilators, antivirals, and antibiotics is well established to treat a variety of pulmonary diseases; however, no inhaled receptor tyrosine kinase (RTK) inhibitors have so far been approved for clinical use despite the key role of RTKs in several pulmonary diseases. We describe a detailed roadmap to identify, optimize, and derisk an inhaled platelet-derived growth factor receptor (PDGFR) inhibitor with extended activity in the lungs.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n In this study, stable isotopes were used to model receptor turnover\n in\u00a0vivo<\/jats:italic>\n , a high-resolution crystal structure was generated to support structure-based drug design and enhancement of both potency and specificity, and critical physicochemical parameters that drive lung retention were identified. Since some RTK inhibitors are linked to adverse interstitial lung disease in humans, we developed a cell painting assay that helped to eliminate compounds with non-specific effects.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n We describe the steps we took to optimize the conditions for nebulized delivery to the deep lung and confirmed that >90% of PDGFR inhibition was maintained for at least 6 hours after nebulization of a 1 mg\/kg dose in rats. Finally, modeling was used to calculate the projected human dose for this molecule.<\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n While the focus of this article is on the identification of an inhaled PDGFR inhibitor, our approach to develop a highly potent inhaled compound that has extended lung retention to minimize systemic effects could be adopted for other RTK drug discovery or lung targeting approaches.<\/jats:p>\n <\/jats:sec>","DOI":"10.1177\/19412711261449635","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T10:53:36Z","timestamp":1778237616000},"page":"283-292","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of an Inhaled Pulmonary Selective PDGFR Inhibitor with Sustained Target Engagement"],"prefix":"10.1177","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6309-7557","authenticated-orcid":false,"given":"Glenn","family":"Marsboom","sequence":"first","affiliation":[{"name":"Pulmonary Hypertension Therapeutic Area, Research & Development, Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianbao","family":"Lu","sequence":"additional","affiliation":[{"name":"Global Discovery Chemistry, Research & Development, Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Hong","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Therapeutic Area, Research & Development, Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Holt","sequence":"additional","affiliation":[{"name":"Preclinical Sciences & Translational Safety, Research & Development, Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makhosi","family":"Edmondson","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Therapeutic Area, Research & Development, Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Hu","family":"Huang","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Therapeutic Area, Research & Development, Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M.","family":"Del Rosario","sequence":"additional","affiliation":[{"name":"Discovery Technologies and Molecular Pharmacology, Research & Development, Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salam","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension Therapeutic Area, Research & Development, Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Wong","sequence":"additional","affiliation":[{"name":"Discovery Technologies and Molecular Pharmacology, Research & Development, Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Harbut","sequence":"additional","affiliation":[{"name":"Discovery Technologies and Molecular Pharmacology, Research & Development, Johnson & Johnson Innovative Medicine, Spring House, Pennsylvania, 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