The epithelial calcium channel TRPV6 promotes the progression of carcinomas, including those of breast and prostate. TRPV6 is thus an important target for cancer treatment. Also, the dysfunction of TRPV6 expressed in the intestine may lead to osteoporosis, suggesting another important therapeutic application.

Little information, however, is available on chemical ligands that modulate the function of TRPV6. We will attempt to develop novel TRPV6 ligands using virtual screening (i.e., based on ligand similarity) and general compound screening (e.g., using natural compound libraries). Most successful compounds will be selected for in vitro tumorigenic studies and for the investigation of TRPV6’s ligand-binding site with photo-reactive tags (see project 10C).

A stable production of large amounts of TRPV6 is the key for success in protein crystallization followed by high-resolution protein structure determination by electron and X-ray crystallography.