Thirty-six patients with type 2 diabetes mellitus (T2DM) were randomized 1:1:1 to receive a once-daily oral dose of placebo or 150 or 300 mg of the dual SGLT1/SGLT2 inhibitor LX4211 for 28 days. Relative to placebo, LX4211 enhanced urinary glucose excretion by inhibiting SGLT2-mediated renal glucose reabsorption; markedly and significantly improved multiple measures of glycemic control, including fasting plasma glucose, oral glucose tolerance, and HbA1c; and significantly lowered serum triglycerides. LX4211 also mediated trends for lower weight, lower blood pressure, and higher glucagon-like peptide-1 levels. In a follow-up single-dose study in 12 patients with T2DM, LX4211 (300 mg) significantly increased glucagon-like peptide-1 and peptide YY levels relative to pretreatment values, probably by delaying SGLT1-mediated intestinal glucose absorption. In both studies, LX4211 was well tolerated without evidence of increased gastrointestinal side effects. These data support further study of LX4211-mediated dual SGLT1/SGLT2 inhibition as a novel mechanism of action in the treatment of T2DM.

Fast pyrolysis is a promising thermochemical technology that breaks down renewable and abundant lignocellulosic biomass into a primary liquid product (bio‐oil) in seconds. The bio‐oil can then be potentially catalytically upgraded into transportation fuels and multiple commodity chemicals. Hemicellulose is one of the three major components of lignocellulosic biomass and is characterized as a group of cell wall polysaccharides that are neither cellulose nor pectin. The composition and structural features of hemicellulose (mixture of different heterogeneous polysaccharides) and different specific hemicellulose polysaccharides are reviewed. Particular focus is then given to reviewing the status of hemicellulose pyrolysis in terms of experimental investigations, reaction mechanisms, and kinetic modeling. For each aspect, recent results, challenges, and future prospects are addressed.

General MethodsUnless stated otherwise, reactions were performed in flame-dried glassware under a nitrogen or an argon environment, using freshly distilled solvents. All other commercially obtained reagents were used as received. Thinlayer chromatography (TLC) was performed using E. Merck silica gel 60 F254 precoated plates (0.25 mm).Visualization of the developed chromatogram was performed by fluorescence quenching, cerium ammonium molybdate stain, or ninhydrin stain as necessary. ICN silica gel (particle size 0.032 -0.063 mm) was used for flash chromatography. Gel filtration chromatography (Sephadex G-10 and G-25 ultrafine) was used in order to achieve purification of the final products.

The discovery of a pyrrolopyrimidine class of LIM-kinase 2 (LIMK2) inhibitors is reported. These LIMK2 inhibitors show good potency in enzymatic and cellular assays and good selectivity against ROCK. After topical dosing to the eye in a steroid induced mouse model of ocular hypertension, the compounds reduce intraocular pressure to baseline levels. The compounds also increase outflow facility in a pig eye perfusion assay. These results suggest LIMK2 may be an effective target for treating ocular hypertension and associated glaucoma.

This work reports the first mechanistic model of fast pyrolysis of hemicellulose that describes detailed pathways of the decomposition of hemicellulose polymeric chains, the reactions of intermediates, and the formation of various experimentally observed products.