A pharmacophore similarity algorithm called xLOS was used in combination with chemical synthesis to entirely change the scaffold of a weak, unselective inhibitor of calcium channel TRPV6 to obtain a potent, selective inhibitor. Inhibition of TRPV6 selectively reduced cancer cell growth.
This virtual screening method may be generally useful to develop tool compounds for poorly characterized targets.

This work was carried out in the group of Prof. Jean-Louis Reymond.

References:

• C. Simonin, M. Awale, M. Brand, R. van Deursen, J. Schwartz, M. Fine, G. Kovacs, P. Häfliger, G. Gyimesi, A. Sithampari, R. P. Charles, M. A. Hediger, J. L. Reymond;
  "Optimization of TRPV6 CalcIium Channel Inhibitors Using a 3D Ligand-Based Virtual Screening Method"
  Angew. Chem., Int. Ed., 2015, 54(49), 14748-14752; doi:10.1002/anie.201507320.