TAK-778, a derivative of ipriflavone, demonstrates the ability to stimulate bone growth in both in vitro and in vivo models.

In vitro and in vivo models, TAK-778 is a derivative of ipriflavone and has been shown to induce bone growth. Continuous treatment with TAK-778 (10 μM) for 1 to 21 days results in an increase in the area of mineralized nodules. TAK-778 at concentrations of 1 μM and higher significantly stimulates the activity of cellular Alkaline phosphatase (ALP). TAK-778 increases slightly but significantly the DNA content of the cells at the confluence stage. Treatment with TAK-778 also results in dose-dependent increases in the amount of soluble collagen and osteocalcin secreted into culture medium from days 5 to 7. the secretion of both TGF-β and IGF-I at every time point during the 21 days of culture enhanced by TAK-778. Treatment of the cells with TAK-778 does not induce ALP activity, but does result in a dose-dependent increase in the saturated cell density. TAK-778(10 μM) significantly reduces the saturated cell density[2].

TAK-778/PLGA-MC (a single local application,0.2 to 5 mg/site) results in a dose-dependent increase in the radio-opaque area formed in the defect. Histological studies show the defect area is occupied by a bony bridge and the newly-formed radio-opaque area corresponds to a calcified bone containing bone marrow cavities surrounded by thick osteoid seams with cuboidal osteoblasts. Two months after the operation, the TAK-778/PLGA-MC pellets induce radiological osseous union across the defects[2]. TAK-778 (Oral treatment of OVX rats)causes a more pronounced increase in bone mineral density (BMD) of the lumbar vertebrae compare to vehicle controls[3].