Cell death plays a pivotal role in the maintenance of tissue homeostasis. Key players in the controlled induction of cell death are the Death Receptors (DR). CD95 is a prototypic DR activated by its cognate ligand CD95L triggering programmed cell death. As a consequence, alterations in the CD95/CD95L pathway have been involved in several disease conditions ranging from autoimmune diseases to inflammation and cancer. CD95L-induced cell death has multiple roles in the immune response since it constitutes one of the mechanisms by which cytotoxic lymphocytes kill their targets, but it is also involved in the process of turning off the immune response. Furthermore, beyond the canonical pro-death signals, CD95L, which can be membrane-bound or soluble, also induces non-apoptotic signaling that contributes to its tumor-promoting and pro-inflammatory roles. The intent of this review is to describe the role of CD95/CD95L in the pathophysiology of cancers, autoimmune diseases and chronic inflammation and to discuss recently patented and emerging therapeutic strategies that exploit/block the CD95/CD95L system in these diseases.

For the first time, chirality in (3 Z,9 Z)-1,2,5,8-dithiadiazecine-6,7(5 H,8 H)-dione series was recognized. Enantiomers of the 4,9-dimethyl-5,8-diphenyl analogue were isolated at room temperature, and their thermal stability was determined. X-ray crystallography confirmed the occurrence of a pair of enantiomers in the crystal. Absolute configurations were assigned by comparing experimental and calculated vibrational/electronic circular dichroism spectra of isolated enantiomers. A distorted tesseract (four-dimensional hypercube) was used to visualize the calculated enantiomerization process, which requires the rotation around four chirality axes. Conformers of higher energy as well as several concurrent pathways of similar energies were revealed.