An orally bioavailable parthenolide analog selectively eradicates acute myelogenous leukemia stem and progenitor cells.

ABSTRACT: Leukemia stem cells (LSCs) are thought to play a central role in the pathogenesis of acute leukemia and likely contribute to both disease initiation and relapse. Therefore, identification of agents that target LSCs is an important consideration for the development of new therapies. To this end, we have previously demonstrated that the naturally occurring compound parthenolide (PTL) can induce death of human LSCs in vitro while sparing normal hematopoietic cells. However, PTL has relatively poor pharmacologic properties that limit its potential clinical use. Consequently, we generated a family of PTL analogs designed to improve solubility and bioavailability. These studies identified an analog, dimethylamino-parthenolide (DMAPT), which induces rapid death of primary human LSCs from both mye

SUBMITTER: Guzman ML 

PROVIDER: S-EPMC2234793 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature