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Current treatments, including platelet transfusions and thrombopoietin receptor agonists, are limited by platelet supply constraints and risks such as thrombotic complications. Emerging research highlights the role of mitochondrial-related biological processes or components in thrombopoiesis, yet targeted therapeutics remain scarce.<\/jats:p>\n                  <jats:p>Methods: In this study, we investigated mitochondria-targeted compounds for their potential to enhance megakaryocyte and platelet productionusing a fetal liver megakaryocyte differentiation and platelet culture system, and explored their effects on in vivo megakaryocyte and platelet production using a radiation damage-induced thrombocytopenia mouse model.<\/jats:p>\n                  <jats:p>Results: Our findings identify PTC299, a dihydroorotate dehydrogenase and VEGFA mRNA translation inhibitor, as a promising pro-plateletogenic agent. PTC299 not only enhances megakaryocyte and platelet production in vitro but also accelerates their recovery in a mouse model of radiation-induced thrombocytopenia. Additionally, PTC299 alleviates irradiation-induced splenomegaly.<\/jats:p>\n                  <jats:p>Conclusion: PTC299 promotes megakaryocyte differentiation and platelet generation both in vitro and in vivo, demonstrating potential values for thrombocytopenia treatment and platelet regeneration.<\/jats:p>","DOI":"10.1093\/stcltm\/szag035","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T12:25:33Z","timestamp":1773663933000},"source":"Crossref","is-referenced-by-count":0,"title":["The mitochondria-targeting compound PTC299 enhances megakaryocyte and platelet production"],"prefix":"10.1093","volume":"15","author":[{"given":"Xiaoli","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Guizhou Medical University , Gui'an New District, Guiyang 561113,","place":["China"]},{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, 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