CCR 20th Anniversary Commentary: Determining a Pharmacokinetic/Pharmacodynamic Relationship for Sunitinib­A Look Back.

The article by Mendel and colleagues, published in the January 1, 2003, issue of Clinical Cancer Research, described their novel preclinical approach to developing a thorough understanding of the exposure-activity relationship for sunitinib, a multitargeted receptor tyrosine kinase inhibitor being developed for oncology therapy. This work successfully set exposure guidelines to identify a biologically active dose in early clinical trials.

Chemistry and biology of roseophilin and the prodigiosin alkaloids: a survey of the last 2500 years.

The pyrrole alkaloids of the prodigiosin family make up an unusual chapter in the chemistry of natural products. Owing to the characteristic red color of these secondary metabolites, colonies of the Gram-negative-producing bacteria may strikingly resemble droplets of blood. This phenomenon caused considerable confusion in the past and was likely responsible for many seemingly miraculous (prodigious) events. After the eventual transition from superstition to science, the prodigiosins started to attract considerable attention because of their promising physiological properties. Most interesting are the immunosuppressive activities at doses that are not cytotoxic, in particular since in vivo studies suggest that the prodigiosins act synergistically with cyclosporine A or FK 506, which are presently the dominant drugs in clinical immunosuppressive regimens. Furthermore, the chemistry of the closely related and structurally rather unique alkaloid roseophilin is summarized, a cytotoxic agent that recently became the focal point of many innovative total syntheses.