dactolisib and Polycystic-Kidney-Diseases

The aim of the present study was to develop folic acid (FA) conjugates which can deliver the kinase inhibitor dactolisib to the kidneys via folate receptor-mediated uptake in tubular epithelial cells. Dactolisib is a dual inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) and is considered an attractive agent for treatment of polycystic kidney disease. The ethylenediamine platinum(II) linker, herein called Lx, was employed to couple dactolisib via coordination chemistry to thiol-containing FA-spacer adducts to yield FA-Lx-dactolisib conjugates. The dye lissamine was coupled via similar linker chemistry to folate to yield fluorescent FA-Lx-lissamine conjugates. Three different spacers (PEG

Topics: Antineoplastic Agents; Cell Line; Drug Liberation; Folic Acid; Humans; Imidazoles; Kidney Tubules; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Polycystic Kidney Diseases; Quinolines; TOR Serine-Threonine Kinases