MBC-11

MBC-11 is a first-in-class conjugate of the bone-targeting bisphosphonate etidronate covalently linked to the antimetabolite cytarabine (araC). Has potential to treat tumor-induced bone disease (TIBD)[1].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

MBC-11 shows similar activity profiles and significantly inhibits growth of all three cell lines between 10-8 and 10-4 M. MBC-11 decreases KAS-6/1 cell growth from approximately 56% at 10-8 M to 6% at 10-5 M[1]. Cell Proliferation Assay[1] Cell Line: Human multiple myeloma cell lines (KAS-6/1, DP-6, KP-6). Concentration: Between 10-8 and 10-4 M. Incubation Time: 48 hours. Result: Significantly inhibited multiple myeloma cell proliferation of each cell line at the majority of the tested concentrations.

MBC-11 (0.04 μg/day, s.c.) has a lower incidence of bone metastases of 40% compared to those treated with PBS (90%) or 0.04 μg/day zoledronate (100%). MBC-11 also significantly decreases bone tumor burden compared to PBS- or zoledronate-treated mice[1]. Weight gained in mice treated with up to 500 μg/day of MBC-11 is similar to the PBS treated group[1]. These results demonstrate that MBC-11 decreases bone tumor burden, maintains bone structure, and may increase overall survival, warranting further investigation as a treatment for tumor-induced bone disease (TIBD)[1]. Animal Model: Approximately four-week old female Balb/c mice inoculated (s.c. injection into their mammary fatpads) with 500,000 4T1/luc cells at day 0 (breast tumor model)[1]. Dosage: 0.04, 0.4, or 4.0 μg/day. Administration: S.C. daily from day 7 to 21. Result: The dose of 0.04 μg/day had a lower incidence of bone metastases compared to those treated with PBS or 0.04 μg/day zoledronate. Animal Model: Female Balb/c and SCID mice (four-six weeks old)[1]. Dosage: 500, 100, 1, or 0.01 μg/100 μL. Administration: S.C. daily for 24 or 49 days. Result: Weight gained in MBC-11 treated mice with different doses was similar to the PBS treated group.

[1]. Reinholz MM, et al. A promising approach for treatment of tumor-induced bone diseases: utilizing bisphosphonate derivatives of nucleoside antimetabolites. Bone. 2010 Jul;47(1):12-22.