Cyclophilin D as a drug target
Cyclophilin D (CYP D), is a member of a family of highly homologous peptidylprolyl cis-trans isomerases (PPIases) that interconvert the cis and trans isomers of peptide bonds with the amino acid proline. Proteins with prolyl isomerase activity include cyclophilins, FKBPs, and parvulin. Inhibitors of Cyclophilin D have been postulated as potential drugs for a variety of therapeutic targets including anti-viral activity DOI, neurodegenration DOI, Cancer DOI etc.
Until recently work in this area suffered from the lack of high quality, selective inhibitors, the best studied being the immunosuppressants Cyclosporin and Sanglifehrin A.
At the recent Macrocycles 2018 meeting Vicky Steadman described the identification and optimisation of potent and orally available selective Cyclophilin inhibitors, more details have just been published J Med Chem paper DOI.
Let's hope with potent, cell penetrant and orally available tools in hand we can sort out the biology and bring forward a new class of therapeutic agents.