Indazole inhibitors of the Wnt signal pathway and therapeutic uses thereof
Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.
1. A compound which is
or a pharmaceutically acceptable salt thereof.
2. A pharmaceutical composition comprising a compound which is
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
3. The pharmaceutical composition of claim 2 , wherein the pharmaceutically acceptable excipient is selected from the group consisting of: saline, a cellulose derivative, a pH buffering agent, and mixtures thereof.
4. The pharmaceutical composition of claim 3 , wherein the pharmaceutically acceptable excipient is selected from the group consisting of: saline, sodium carboxymethyl cellulose (CMC), a phosphate buffering agent, and mixtures thereof.
5. The pharmaceutical composition of claim 2 , wherein the composition is a liquid composition.
6. The pharmaceutical composition of claim 2 , wherein the composition is an emulsion.
7. The pharmaceutical composition of claim 2 , wherein the composition is a suspension.
8. The pharmaceutical composition of claim 2 , wherein the composition is formulated for intra-articular administration.
9. A suspension composition comprising a compound which is
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
10. The suspension composition of claim 9 , wherein the pharmaceutically acceptable excipient is selected from the group consisting of: saline, a cellulose derivative, a pH buffering agent, a tween, and mixtures thereof.
11. The suspension composition of claim 10 , wherein the pharmaceutically acceptable excipient is selected from the group consisting of: saline, sodium carboxymethyl cellulose (CMC), a phosphate buffering agent, Tween 80, and mixtures thereof.
12. The suspension composition of claim 11 , wherein the composition is 0.5% CMC/0.05% Tween 80 in a phosphate-buffered saline (PBS) solution at pH 7.4.
13. The suspension composition of claim 12 , wherein the composition is formulated for intra-articular administration.
14. The intra-articular administration of claim 13 , wherein the administration is combined with one or more of nonsteroidal anti-inflammatory drugs (NSAIDs), injections of corticosteroid medications, injections of hyaluronic acid derivatives, or narcotics.
15. A method of treating osteoarthritis in a mammal, the method comprising intra-articularly administering to the mammal a therapeutically effective amount of a compound, having the structure of:
or a pharmaceutically acceptable salt thereof.
16. A method of treating osteoarthritis in a mammal, the method comprising intra-articularly administering to the mammal a therapeutically effective amount of a pharmaceutical composition comprising a compound having the structure of:
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
17. The method of claim 15 , wherein the mammal is a human.
18. The method of claim 16 , wherein the mammal is a human.