Biological activities of fusarochromanone: a potent anti-cancer agent.

Background: Fusarochromanone (FC101) is a small molecule fungal metabolite with a host of interesting biological functions, including very potent anti-angiogenic and direct anti-cancer activity.

Results: Herein, we report that FC101 exhibits very potent in-vitro growth inhibitory effects (IC50 ranging from 10nM-2.5 μM) against HaCat (pre-malignant skin), P9-WT (malignant skin), MCF-7 (low malignant breast), MDA-231 (malignant breast), SV-HUC (premalignant bladder), UM-UC14 (malignant bladder), and PC3 (malignant prostate) in a time-course and dose-dependent manner, with the UM-UC14 cells being the most sensitive.

Contribution of ABCC4-mediated gastric transport to the absorption and efficacy of dasatinib.

Purpose: Several oral multikinase inhibitors are known to interact in vitro with the human ATP-binding cassette transporter ABCC4 (MRP4), but the in vivo relevance of this interaction remains poorly understood. We hypothesized that host ABCC4 activity may influence the pharmacokinetic profile of dasatinib and subsequently affect its antitumor properties.

Experimental Design: Transport of dasatinib was studied in cells transfected with human ABCC4 or the ortholog mouse transporter, Abcc4.

Phase I pharmacokinetic and pharmacodynamic study of the multikinase inhibitor sorafenib in combination with clofarabine and cytarabine in pediatric relapsed/refractory leukemia.

Purpose: To assess the toxicity, pharmacokinetics, and pharmacodynamics of multikinase inhibitor sorafenib in combination with clofarabine and cytarabine in children with relapsed/refractory leukemia.

Patients And Methods: Twelve patients with acute leukemia (11 with acute myeloid leukemia [AML]) received sorafenib on days 1 to 7 and then concurrently with cytarabine (1 g/m(2)) and clofarabine (stratum one: 40 mg/m(2), n = 10; stratum two [recent transplantation or fungal infection]: 20 mg/m(2), n = 2) on days 8 to 12. Sorafenib was continued until day 28 if tolerated.

Differential uptake and selective permeability of fusarochromanone (FC101), a novel membrane permeable anticancer naturally fluorescent compound in tumor and normal cells.

The differential accumulation of fluorescent molecules in tumorigenic versus normal cells is a well-reported phenomenon and is the basis for photodiagnostic therapy. Through the use of confocal microscopy, the kinetic uptake and accumulation of fusarochromanone (FC101) was determined in two lines of living tumorigenic cells of mesenchymal-epithelial origin and normal fibroblast cells. Like other fluorescent cationic molecules, FC101 showed increased accumulation in tumorigenic cells; however, unlike other molecules, it appeared to be accumulated in a time-dependent manner.