Portal de Periódicos da CAPES

An image-based screen identifies a small molecule regulator of megakaryopoiesis

2012; National Academy of Sciences; Volume: 109; Issue: 35 Linguagem: Inglês

10.1073/pnas.1212545109

1091-6490

Anthony E. Boitano, Lorenzo de Lichtervelde, Jennifer L. Snead, Michael P. Cooke, Peter G. Schultz,

Hematopoietic Stem Cell Transplantation

Molecules that control the lineage commitment of hematopoietic stem cells (HSCs) may allow the expansion of enriched progenitor populations for both research and therapeutic uses. In an effort to better understand and control the differentiation of HSCs to megakaryocytes, we carried out an image-based screen of a library of 50,000 heterocycles using primary human CD34 + cells. A class of naphthyridinone derivatives was identified that induces the differentiation of common myeloid progenitors (CMP) to megakaryocytes. Kinase profiling and subsequent functional assays revealed that these compounds act through inhibition of platelet-derived growth factor receptor (PDGFR) signaling in CMPs. Such molecules may ultimately have clinical utility in the treatment of thrombocytopenia.