This review highlights the past six year advances in the blossoming field of cucurbit[n]uril chemistry. Because of their exceptional recognition properties in aqueous medium, these pumpkin-shaped macrocycles have been generating some tremendous interest in the supramolecular community. They have also become key units in various self-organizing and stimulus-controlled assemblies, as well as in advanced materials and drug carriers. The scope of this review is limited to the main family of cucurbit[n]urils (n = 5, 6, 7, 8, 10). The reader will find an overview of their preparation, their physicochemical and biological properties, as well as their recognition abilities towards various organic and inorganic guests. Detailed thermodynamic and kinetic considerations, as well as multiple applications including supramolecular catalysis are also discussed.

Purpose: LBH589 is a novel histone deacetylase inhibitor that inhibits proliferation and induces apoptosis in tumor cell lines. In this phase I study, LBH589 was administered i.v. as a 30-minute infusion on days 1to 7 of a 21-day cycle. Experimental Design: Fifteen patients (median age, 63 years; range, 42-87 years) with acute myeloid leukemia (13 patients), acute lymphocytic leukemia (1 patient), or myelodysplastic syndrome (1 patient) were treated with LBH589 at the following dose levels (mg/m 2 ): 4.8 (3 patients), 7.2 (3 patients), 9.0 (1patient), 11.5 (3 patient), and 14.0 (5 patients). The levels of histone acetylation were measured using quantitative flow cytometry and plasma LBH589 concentrations were assayed. Results: Four dose-limiting toxicities (grade 3 QTcF prolongation) were observed, four at 14.0 mg/m 2 and one at 11.5 mg/m 2 . QTcF prolongation was asymptomatic and reversed on LBH589 discontinuation. Other potentially LBH589-related toxicities included nausea (40%), diarrhea (33%), vomiting (33%), hypokalemia (27%), loss of appetite (13%), and thrombocytopenia (13%). In 8 of 11 patients with peripheral blasts, transient reductions occurred with a rebound following the 7-day treatment period. H3 acetylation increase was significant in B-cells (CD19

Purpose: This retrospective analysis was conducted to characterize ipilimumab exposure-response relationships for measures of efficacy and safety in patients with advanced melanoma.Experimental Design: Data were pooled from 498 patients who received ipilimumab monotherapy at 0.3, 3, or 10 mg/kg in 1 of 4 completed phase II clinical trials. The relationships between steady-state ipilimumab trough concentration (Cminss), complete or partial tumor response (CR or PR), and safety [immune-related adverse events (irAEs)] were described by logistic regression models. The relationship between exposure and overall survival was characterized using a Cox proportional-hazards model.Results: The steady-state trough concentration of ipilimumab was found to be a significant predictor of a CR or PR (P < 0.001). Model-based estimates indicate that the probabilities of a CR or PR at median Cminss for the 0.3, 3, and 10 mg/kg groups were 0.6%, 4.9%, and 11.6%, respectively. Overall survival at the median Cminss for ipilimumab at 0.3 mg/kg was estimated to be 0.85-and 0.58-fold lower relative to that at the median Cminss for 3 and 10 mg/kg, respectively. Model-based estimates indicate that the probabilities of a grade 3 or more irAE at the median Cminss for the 0.3, 3, and 10 mg/kg doses were 3%, 13%, and 24%, respectively.Conclusions: Higher doses of ipilimumab produce greater Cminss that may be associated with increased tumor responses, longer survival, and higher rates of irAEs. The efficacy and safety of ipilimumab at 3 versus 10 mg/kg in patients with advanced melanoma is being evaluated in an ongoing phase III trial.