HP-β-CD

HP-β-CD ((2-Hydroxypropyl)-β-cyclodextrin) is a widely used drug delivery vehicle to improve the stability and bioavailability. In Vitro: Cell treatment with HP-β-CD results in the activation of the transcription factor EB, a master regulator of lysosomal function and autophagy, and in enhancement of the cellular autophagic clearance capacity^[1]. HP-β-CD treatment reduces intracellular cholesterol resulting in significant leukemic cell growth inhibition through G2/M cell-cycle arrest and apoptosis. The IC₅₀ values for HP-β-CD after 72 hours exposure are in the range of 3.86-10.09 mM. HP-β-CD also shows anticancer effects against CML cells expressing a T315I BCR-ABL mutation (that confers resistance to most ABL tyrosine kinase inhibitors), and hypoxia-adapted CML cells that have characteristics of leukemic stem cells. In addition, colony forming ability of human primary AML and CML cells is inhibited by HP-β-CD^[2]. In Vivo: HP-β-CD administration promotes transcription factor EB-mediated clearance of proteolipid aggregates that accumulate due to inefficient activity of the lysosome-autophagy system in cells derived from a patient with a lysosomal storage disorder^[1]. Intraperitoneal injection of HP-β-CD significantly improves survival in leukemia mouse models. Systemic administration of HP-β-CD to mice has no significant adverse effects^[2].