| 16250659 |
Sohoel H, Liljefors T, Ley SV, Oliver SF, Antonello A, Smith MD, Olsen CE, Isaacs JT, Christensen SB: Total synthesis of two novel subpicomolar sarco/endoplasmatic reticulum Ca2+-ATPase inhibitors designed by an analysis of the binding site of thapsigargin. J Med Chem. 2005 Nov 3;48(22):7005-11.
Analysis of molecular interaction fields based on the published crystal structure of thapsigargin bound to the sarco/endoplasmatic reticulum Ca (2+)-ATPase and analysis of the volume and shape of the ligand binding site and of the SERCA-thapsigargin interactions have enabled design of two new compounds inhibiting SERCA in the subpicomolar range. The two inhibitors were synthesized using (S)-carvone as starting material and found to be 3 and 10 times more potent than thapsigargin. |
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