RIDR-PI-103

RIDR-PI-103 is a reactive oxygen species (ROS)-activated prodrug of the PI3K inhibitor PI-103. It features a self-cyclizing moiety linked to PI-103 that triggers drug release specifically under conditions of high oxidative stress, which are often present in melanoma cells that have acquired resistance to BRAF and MEK inhibitors. By releasing PI-103 locally, the drug inhibits the PI3K/Akt pathway (specifically the conversion of PIP2 to PIP3) and downstream signaling (p-Akt, p-S6), thereby inhibiting cell proliferation in resistant BRAF-mutant melanoma models while exhibiting reduced toxicity in normal melanocytes.