An update into the medicinal chemistry of translocator protein (TSPO) ligands.

An update into the medicinal chemistry of translocator protein (TSPO) ligands. Eur J Med Chem. 2020 Oct 14;:112924 Authors: Barresi E, Robello M, Costa B, Da Pozzo E, Baglini E, Salerno S, Da Settimo F, Martini C, Taliani S Abstract The Translocator Protein 18 kDa (TSPO) has been discovered in 1977 as an alternative binding site for the benzodiazepine diazepam. It is an evolutionary well-conserved and tryptophan-rich 169-amino acids protein with five alpha helical transmembrane domains stretching the outer mitochondrial membrane, with the carboxyl-terminus in the cytosol and a short amino-terminus in the intermembrane space of mitochondrion. At this level, together with the voltage-dependent anion channel (VDAC) and the adenine nucleotide translocase (ANT), it forms the mitochondrial permeability transition pore (MPTP). TSPO expression is ubiquitary, with higher levels in steroid producing tissues; in the central nervous system, it is mainly expressed in glial cells and in neurons. TSPO is implicated in a variety of fundamental cellular processes including steroidogenesis, heme biosynthesis, mitochondrial respiration, mitochondrial membrane potential, cell proliferation and differentiation, cell life/death balance, oxidative stress. Altered TSPO expression has been found in some pathological conditions. In particular, high TSPO expression levels have been documented in cancer, neuroinflammation, and brain injury. Conversely, low TSP...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Tags: Eur J Med Chem Source Type: research