Efficacy and Safety of RelabotulinumtoxinA, a New Ready-to-Use Liquid Formulation Botulinum Toxin: Results From the READY-1 Double-Blind, Randomized, Placebo-Controlled Phase 3 Trial in Glabellar Lines.

Background: RelabotulinumtoxinA (RelaBoNT-A, Galderma, Uppsala, Sweden) is an innovative, ready-to-use liquid botulinum toxin A, produced with PEARL (precipitation-free extraction and activity-preserving refined liquid) manufacturing technology, which yields a potent, complex-free formulation.

Objectives: In the READY-1 study, efficacy and safety outcomes following a single RelaBoNT-A treatment for glabellar line correction were examined.

Methods: Adults with moderate to severe glabellar lines received RelaBoNT-A (50 U) or placebo in a 3:1 randomized, 6-month, phase 3, multicenter, double-blind study.

N-Benzyl-indolo carboxylic acids: Design and synthesis of potent and selective adipocyte fatty-acid binding protein (A-FABP) inhibitors.

Small molecule inhibitors of adipocyte fatty-acid binding protein (A-FABP) have gained renewed interest following the recent publication of pharmacologically beneficial effects of such inhibitors. Despite the potential utility of selective A-FABP inhibitors within the fields of metabolic disease, inflammation and atherosclerosis, there are few examples of useful A-FABP inhibitors in the public domain. Herein, we describe the optimization of N-benzyl-tetrahydrocarbazole derivatives through the use of co-crystal structure guided medicinal chemistry efforts.

Substituted benzylamino-6-(trifluoromethyl)pyrimidin-4(1H)-ones: a novel class of selective human A-FABP inhibitors.

The synthesis and biological evaluation of novel human A-FABP inhibitors based on the 6-(trifluoromethyl)pyrimidine-4(1H)-one scaffold is described. Two series of compounds, bearing either an amino or carbon substituent in the 2-position of the pyrimidine ring were investigated. Modification of substituents and chain length optimization led to novel compounds with low micromolar activity and good selectivity for human A-FABP.

Discovery of inhibitors of human adipocyte fatty acid-binding protein, a potential type 2 diabetes target.

Low micromolar human A-FABP inhibitors were found by utilizing a fluorescence polarization assay, X-ray crystallography and modeling. The carbazole- and indole-based inhibitors displayed approximately 10-fold preferences over human H-FABP and E-FABP, and are highly selective against I-FABP. This communication describes the SAR for drug-like synthetic inhibitors of human A-FABP.