Tuning the Reactivity of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activators for Optimal Efficacy.

Dimethyl fumarate is approved for the treatment of multiple sclerosis but is also associated with off-target activation of the niacin receptor. By using a tetrazolone or triazolone bioisostere approach to the fumarate and vinyl sulfone series of Nrf2 activators, we have optimized the electrophilicity of the double bond to tune the on-target Nrf2 activation with PK properties to achieve efficacy in animal models of multiple sclerosis. The study linked highly potent, highly electrophilic molecules to low plasma stability and, subsequently, limited efficacy.

Flowers of Apocynaceae in amber from the early Eocene of India.

Premise: Early Eocene ambers of the Cambay lignite in Gujarat, India, are well known for their diverse insect fauna and dispersed pollen, but the included flowers have received limited attention. The fossil record of Apocynaceae is relatively poor, and the distinctive floral characters of this family have not been recognized in the fossil record before.

Methods: Remains of tiny flowers in amber were studied by micro-CT scanning, reflected light, and epifluorescence microscopy.

Thermoluminescence study in fossils of dinosaur bones and eggshells.

In this study, thermoluminescence (TL) characterization of fossils of sauropod dinosaur bone, dinosaur eggshells, and associated sediments were recorded for the first time. The fossil bone was collected from the Bagwanya intertrappean sediments in the Dhar district of Madhya Pradesh, India. TL was recorded using Co gamma ray exposure at different doses.

Study of thermoluminescence in turtle shell fossils using radiation dosimetry.

The present study describes for the first time thermoluminescence (TL) characterization of turtle shell. A fossil shell was collected from the Dongargaon area in the Chandrapur district of Maharashtra, India. TL was recorded and a comparative study of TL for the above material was performed to understand the special TL characteristics of the shell.

Orally available and efficacious α4β1/α4β7 integrin inhibitors.

A series of potent α4β1/α4β7 integrin inhibitors is reported, including an inhibitor 12d with remarkable oral exposure and efficacy in rat models of rheumatoid arthritis and Crohn's disease.