BISPHOSPHONATE-PROSTATIC ACID PHOSPHATASE INHIBITOR CONJUGATES TO TREAT PROSTATE CANCER BONE METASTASIS
The present invention concerns conjugate compounds comprising a bisphosphonate covalently bonded to a prostatic acid phosphatase inhibitor and compositions comprising such conjugates. Methods for treating and inhibiting prostate cancer bone metastases, and determining whether a conjugate is useful for such treatment are also provided. In some instances, the bisphosphonate is alendronate, and it is covalently bonded to either tartaric acid or glyceric acid.
1 . A compound comprising a bisphosphonate covalently bonded to a prostatic acid phosphatase (PAP) inhibitor, or a pharmaceutically acceptable salt thereof.
2 . The compound of claim 1 , wherein the bisphosphonate is alendronate.
3 . The compound of claim 1 , wherein the prostatic acid phosphatase (PAP) inhibitor is tartrate or glyceric acid.
4 . The compound of claim 1 that is N-Alendronyl-L-Tartaric Acid Monamide.
5 . The compound of claim 1 that is N-Alendronyl-D-Glyceramide.
6 . A composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.
7 . A method for inhibiting prostate cancer bone metastasis in a subject in need thereof, comprising, administering to the subject an effective amount of the compound of claim 1 .
8 . The method of claim 7 , comprising administering the compound in a composition comprising a pharmaceutically acceptable excipient.
9 . The method of claim 8 , wherein the method comprises oral administration of the composition.
10 . The method of claim 8 , wherein the method comprises parenteral administration of the composition.
11 . A method for treating prostate cancer bone metastasis in a subject in need thereof, comprising: administering to the subject an effective amount of the compound of claim 1 .
12 . The method of claim 11 , comprising administering the compound in a composition comprising a pharmaceutically acceptable excipient.
13 . The method of claim 12 , wherein the method comprises oral administration of the composition.
14 . The method of claim 12 , wherein the method comprises parenteral administration of the composition.
15 . A method for inhibiting the activity of PAP in a subject in need thereof, comprising administering to the subject, an effective amount of the compound of claim 1 .
16 . The method of claim 15 , comprising administering the compound in a composition comprising a pharmaceutically acceptable excipient.
17 . A method for making a PAP inhibitor orally active, comprising covalently bonding the PAP inhibitor to a bisphosphonate.
18 . The method of claim 17 , wherein the bisphosphonate is alendronate and the PAP inhibitor is selected from tartaric acid and glyceric acid.