1 A-Hydroxyvitamin D5 as a Chemotherapeutic and Possibly Chemopreventive Agent
Abstract
We identified a novel vitamin D analog, la-hydroxy-24 ethyl vitamin D5 (1alpha(OH)D5) that showed potent growth inhibitory and cell-differentiating actions in breast cancer cells. Based On our findings in vitro and in vivo, we hypothesized that 1alpha(0H)Ds(D5)when administered to women with breast cancer, will induce differentiation of dedifferentiated cells and thereby prevent progression of malignancy. 1999-2000, we completed preclinical studies in rats, showing that D5 has no serious toxicity; a hypercalcemic effect was observed at high dose, which was reversible. In vitro study in tissues obtained from patients show that D5 has no effect on normal breast epithelial cells but induces apoptosis in breast cancer and showed apoptotic effect in fibroadenomas. We completed 5 steps in the synthesis of D5in preparation for phase I clinical study. 2001-2002, under GMP, we completed preclinical toxicity studies in dogs and completed synthesis of 1alpha(OH)D5 . In vitro studies in clinical specimens suggest that D5 has-no effect on normal breast tissues; it inhibits cell proliferation in tumor cells. D5 or its active metabolite possibly interacts with estrogen receptor. 2002-2003, all the requirements for the clinical trial are completed; we submitted an application for IND to FDA. The FDA responded back with a few questions. These have been completed and the revised application is once again submitted. We will initiate studies as soon as the approval is granted. In the present report we have included the clinical portion of the brochure, since the summary of results on the efficacy and mechanism of action of 1alpha(OH)D5 were submitted in previous years.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2003
- Accession Number
- ADA420118
Entities
People
- Tepas K. Das Gupta
Organizations
- University of Illinois at Chicago