Novel Bisphosphonates for Multiple Myeloma Therapy

DESCRIPTION (provided by applicant): Bisphosphonates are currently used as bone-specific palliative treatments for the tumor-induced bone diseases observed in breast cancer and multiple myeloma patients. However, bisphosphonate use has no proven impact on primary tumor burden and overall survival and only moderately reduces skeletal complications. Bisphosphonate conjugates were synthesized using proprietary technology that employs a unique chemical bridge between anti-cancer (nucleotide analogs) or vitamin B( moieties and a bisphosphonate backbone. The nucleotide-bisphosphonate conjugates were designed to deliver anti-cancer agents and bone-protecting bisphosphonates specifically to bone. The vitamin B6 conjugates were designed to increase the cellular uptake of bisphosphonates. Results from preliminary in vitro studies demonstrated increased anti-tumor efficacy of select conjugates compared to the anti-cancer or bisphosphonate compounds alone. The overall aim of this project is to further develop bisphosphonate conjugate technology and to determine the effects of these compounds on bone loss, tumor burden, and survival in an established animal model of multiple myeloma. Successful development of this new drug-design concept would provide a biologically and commercially superior approach for the treatment and prevention of skeletal-related complications of malignancy.