7 research outputs found
Incorporation of ABCB1-mediated transport into a physiologically-based pharmacokinetic model of docetaxel in mice
Visualizing spatial distribution of alectinib in murine brain using quantitative mass spectrometry imaging
Effect of triacontanol on the pharmacokinetics of docetaxel in rats associated with induction of cytochrome P450 3A1/2
A Whole-Body Physiologically Based Pharmacokinetic Model of Gefitinib in Mice and Scale-Up to Humans
Simulation of the pharmacokinetics of bisoprolol in healthy adults and patients with impaired renal function using whole-body physiologically based pharmacokinetic modeling
PI-88 and related heparan sulfate mimetics
The heparan sulfate mimetic PI-88 (muparfostat) is a complex mixture of sulfated oligosaccharides that was identified in the late 1990s as a potent inhibitor of heparanase. In preclinical animal models it was shown to block angiogenesis, metastasis and tumor growth, and subsequently became the first heparanase inhibitor to enter clinical trials for cancer. It progressed to Phase III trials but ultimately was not approved for use. Herein we summarize the preparation, physicochemical and biological properties of PI-88, and discuss preclinical/clinical and structure-activity relationship studies. In addition, we discuss the PI-88-inspired development of related HS mimetic heparanase inhibitors with improved properties, ultimately leading to the discovery of PG545 (pixatimod) which is currently in clinical trials