{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:32:06Z","timestamp":1791981126233,"version":"4.4.0"},"reference-count":75,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gossamer Bio, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) is a complex disorder characterized by vascular remodeling and a consequent increase in pulmonary vascular resistance. The histologic hallmarks of PAH include plexiform and neointimal lesions of the pulmonary arterioles, which are composed of dysregulated, apoptosis-resistant endothelial cells and myofibroblasts. Platelet-derived growth factor receptors (PDGFR) \u03b1 and \u03b2, colony stimulating factor 1 receptor (CSF1R), and mast\/stem cell growth factor receptor kit (c-KIT) are closely related kinases that have been implicated in PAH progression. In addition, emerging data indicate significant crosstalk between PDGF signaling and the bone morphogenetic protein receptor type 2 (BMPR2)\/transforming growth factor \u03b2 (TGF\u03b2) receptor axis. This review will discuss the importance of the PDGFR-CSF1R-c-KIT signaling network in PAH pathogenesis, present evidence that the inhibition of all three nodes in this kinase network is a potential therapeutic approach for PAH, and highlight the therapeutic potential of seralutinib, currently in development for PAH, which targets these pathways.<\/jats:p>","DOI":"10.3390\/ijms241612653","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T10:11:22Z","timestamp":1691662282000},"page":"12653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Pharmacology and Rationale for Seralutinib in the Treatment of Pulmonary Arterial Hypertension"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0440-8831","authenticated-orcid":false,"given":"Soni Savai","family":"Pullamsetti","sequence":"first","affiliation":[{"name":"Lung Vascular Epigenetics, Center for Infection and Genomics of the Lung (CIGL), Justus-Liebig-Universit\u00e4t Gie\u00dfen, Aulweg 132, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravikumar","family":"Sitapara","sequence":"additional","affiliation":[{"name":"Gossamer Bio, Inc., San Diego, CA 92121, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1146-9915","authenticated-orcid":false,"given":"Robin","family":"Osterhout","sequence":"additional","affiliation":[{"name":"Gossamer Bio, Inc., San Diego, CA 92121, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Weiss","sequence":"additional","affiliation":[{"name":"UGMLC Pulmonale Pharmakotherapie, Biomedizinisches Forschungszentrum Seltersberg (BFS), Justus-Liebig-Universit\u00e4t Gie\u00dfen, Schubertstra\u00dfe 81, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L.","family":"Carter","sequence":"additional","affiliation":[{"name":"Gossamer Bio, Inc., San Diego, CA 92121, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence S.","family":"Zisman","sequence":"additional","affiliation":[{"name":"Gossamer Bio, Inc., San Diego, CA 92121, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5167-6970","authenticated-orcid":false,"given":"Ralph Theo","family":"Schermuly","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Justus-Liebig-University Giessen, Aulweg 130, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2200879","DOI":"10.1183\/13993003.00879-2022","article-title":"2022 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension","volume":"61","author":"Humbert","year":"2023","journal-title":"Eur. 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