A new chemical entity, ENMD-1198 is based on a modified chemical structure of 2-methoxyestradiol (2ME2) and is designed to decrease metabolism while retaining 2ME2’s multiple mechanisms of action. These actions include inducing apoptosis, binding microtubules, and inhibiting HIF-1alpha.
Study results demonstrated that ENMD-1198 is an orally active, microtubule disrupting agent that leads to arrest of cell division and apoptosis in tumor cells. In addition, ENMD-1198 also exerts antiangiogenic activity that further contributes to its overall antitumor effects. Preclinical results for ENMD- 1198 support its potential for broad application in cancer.
Data demonstrate that oral administration of ENMD-1198 leads to pronounced in vivo antitumor activity in preclinical cancer models resulting in a reduction in tumor burden and/or an increase in survival equivalent to cyclophosphamide.
Oral daily treatment with ENMD-1198 in an orthotopic animal model of human breast cancer led to the disruption of microtubules within tumor cells, as well as a substantial decrease in tumor cell proliferation and angiogenesis.