5-benzylglycinyl amiloride

UCD38B (5-benzylglycinyl amiloride) is a cell-permeant amiloride derivative developed by researchers at the University of California, Davis (UC Davis) as an anticancer small molecule. It acts as a competitive enzymatic inhibitor of intracellular urokinase-type plasminogen activator (uPA). Unlike its cell-impermeant congener UCD74A, UCD38B is highly cytotoxic to both proliferating and non-proliferating cancer cells, including high-grade glioma (glioblastoma) and breast cancer cells. UCD38B works by binding to intracellular uPA, which disrupts its interaction with plasminogen activator inhibitor-1 (PAI-1) and the endosomal LRP-1 guidance protein. This leads to the "mis-trafficking" of early and late endosomes containing the urokinase plasminogen activator system (uPAS) cargo to perinuclear mitochondrial regions. This endosomal relocation triggers mitochondrial depolarization, organelle swelling (endoplasmic reticulum and mitochondria), and the subsequent release and nuclear translocation of apoptosis-inducing factor (AIF), culminating in caspase-independent programmed necrotic cell death (necroptosis).

Other names

5-benzylglycinyl amiloride5-benzylglycinyl-amilorideSML 0821SML0821SML-0821