lan R. Hardcastle*, Martin G. Rowlands and Michael Jarman Pages 211 - 226 ( 16 )
Antiestrogens are widely used in the treatment of hormone dependent breast cancer. Their principle mechanism of action is believed to be the displacement of the growth promoting hormone estrogen from its protein receptor. Many antiestrogens also exhibit hormone independent effects, such as antagonism of the calcium binding protein calmodulin, which may contribute to their therapeutic potential.
Calmodulin is essential to many cellular processes including the functioning of the estrogen receptor. The- possibility that a combined antiestrogen - calmodulin antagonist would be useful for cancer therapy has led to the development of antiestrogens which are potent calmodulin antagonists.
This review describes the structure - activity relationships for calmodulin antagonists, the rational design of such compounds and their biological properties. The synthetic methodology for some of these antiestrogens will also be discussed.