fimepinostat (Curis, Inc.)

Fimepinostat (CUDC-907) is an orally bioavailable, first-in-class small molecule dual inhibitor of class I and II histone deacetylases (HDACs) and class I phosphoinositide 3-kinase (PI3K) isoforms (specifically PI3Kα, PI3Kβ, and PI3Kδ). Developed by Curis, fimepinostat has been evaluated in clinical trials for various hematological malignancies, including relapsed or refractory diffuse large B-cell lymphoma (DLBCL), and solid tumors such as pediatric brain tumors (e.g., diffuse intrinsic pontine glioma) and thyroid cancer. By simultaneously targeting HDAC and PI3K pathways, fimepinostat synergistically suppresses tumor cell proliferation, downregulates MYC transcription, and induces apoptosis. Additionally, preclinical studies have shown that fimepinostat can pharmacologically upregulate monoamine transporters (such as the norepinephrine transporter, NET) to enhance the tumor uptake of radiopharmaceuticals like 123I-mIBG, suggesting potential utility in advancing theranostics for neuroendocrine tumors.