Computational molecular docking assessment of hormone receptor adjuvant drugs: Breast cancer as an example.

For the maintenance therapy of breast cancer, drugs which act as antagonists/partial agonists of hormone receptors against the breast tissue are used in the conventional clinical practices. However, during the course of treatment the patients may encounter systems related complications. Drugs like tamoxifen, which block the action of estrogens at its receptors in mammary gland; and the recently designed antiestrogens and selective estrogen receptor modulators (SERM) like raloxifene, toremifene and the progesterone antagonist mifepristone (RU-486) are used in the treatment for estrogen and/or progesterone receptor positive breast tumors. These drugs show, however, both acute and long-term toxicity like endometrial hyperplasia and cancer, menopausal symptoms, edema, thromboembolic events like pulmonary embolism and so on. Using molecular docking method, we studied the binding of these drugs at an array of receptors present within the physiological system. In addition, the molecular basis of the antiglucocorticoid and antiandrogenic side effects of mifepristone have also been studied. Our results show weak to moderate binding of these drugs at various receptors of the body. This may explain the toxicity and pathophysiological shifting by these drugs during the long term use of these drugs.