Activation of the mammalian target of rapamycin (mTOR) signaling pathway is aberrant in
autosomal-dominant polycystic kidney disease (ADPKD). The mTOR inhibitors, such as
rapamycin, ameliorate PKD in rodent models, but clinical trials have not shown benefit,
possibly as a result of low tissue concentrations of rapamycin at clinically tolerable doses. To
overcome this limitation, we synthesized a folate-conjugated form of rapamycin (FC-rapa)
that is taken up by folate receptor–mediated endocytosis and cleaved intracellularly to …