Oxysterol analogue OXY133 induces osteogenesis and hedgehog signaling and inhibits adipogenesis
This invention relates, e.g., to a synthetic compound, Oxy133, having the structure [Formula I] or a bioactive or pharmaceutical composition comprising Oxy133 and a pharmaceutically acceptable carrier. Methods are also disclosed for using the compound or bioactive or pharmaceutical composition to treat a variety of disorders, including e.g. bone disorders, obesity, cardiovascular disorders, and neurological disorders.
1. A compound having the structure:
or a pharmaceutically acceptable salt or solvate thereof.
2. A composition, comprising a pharmaceutically acceptable carrier and a compound having the structure:
or a pharmaceutically acceptable salt or solvate thereof.
3. The composition of claim 2 , further comprising at least one additional agent, selected from the group consisting of parathyroid hormone, sodium fluoride, insulin-like growth factor I (ILGF-I), insulin-like growth factor II (ILGF-II), transforming growth factor beta (TGF-β), a cytochrome P450 inhibitor, an osteogenic prostanoid, BMP 2, BMP 4, BMP 7, BMP 14, and combinations thereof.
4. A method for treating a subject having a bone disorder, osteoporosis, or a bone fracture, comprising administering to the subject an effective amount of the composition of claim 2 .
5. The method of claim 4 , comprising administering to the subject the composition at a therapeutically effective dose in an effective dosage form at a selected interval to increase bone mass.
6. The method of claim 4 , comprising administering to the subject the composition at a therapeutically effective dose in an effective dosage form at a selected interval to ameliorate the symptoms of osteoporosis.
7. A method for treating a subject in need of an increase in osteomorphogenesis and/or osteoproliferation, comprising administering to the subject an effective amount of the composition of claim 2 .
8. A method for treating a subject to induce bone formation, comprising administering the composition of claim 2 in an effective dosage form at a selected interval to increase bone mass.
9. The method of claim 4 , wherein the composition is administered locally to a cell, tissue or organ in the subject.
10. An implant for use in a human or animal body comprising a substrate having a surface, wherein the surface or the insides of the implant comprises the composition of claim 2 in an amount sufficient to induce bone formation in the surrounding bone tissue.
11. The implant of claim 10 , wherein the substrate is formed into the shape of a pin, screw, plate, or prosthetic joint.