Inhibitors of 17β-HSD7 and uses thereof
Novel chemical agents are described herein. More specifically, a novel inhibitor of 17β-HSD7 for decreasing estradiol concentrations while restoring dihydrotestosterone (DHT) concentrations in breast cancer cells is disclosed herein. In a particular embodiment, the inhibitor of 17β-HSD7 has the following structure: (Formula I) A process for producing the novel inhibitors of 17β-HSD7 and their use in the manufacture of pharmaceutical formulations and/or combinations is also disclosed.
1 . A 17β-hydroxysteroid dehydrogenase 7 (17β-HSD7) inhibitor compound of Formula I:
or a pharmaceutically acceptable salt or solvate thereof, wherein, R is C ≤12 alkyl or C ≤12 cycloalkyl; and X is O or S.
2 . The inhibitor of claim 1 , having the structure:
3 . A method of treating breast cancer in a subject in need thereof, comprising administering to the subject, the 17β-HSD7 inhibitor compound of claim 1 .
4 . The method of claim 3 , wherein the cancer is an estrogen-sensitive cancer.
5 . The method of claim 3 , further comprising treating the subject with a secondary cancer therapy.
6 . The method of claim 5 , wherein the secondary cancer therapy is selected from the group consisting of chemotherapy, toxin therapy, radiation therapy, hormone or anti-hormone therapy, surgery, cryotherapy, or immunotherapy.
7 . The method of claim 3 , further comprising administering the inhibitor at least a second time.
8 . The method of claim 3 , wherein the inhibitor is administered intravenously, intra-arterially, subcutaneously, topically, or intramuscularly.
9 . The method of claim 3 , wherein the inhibitor is administered systemically, regionally, locally or intratumorally.
10 . The method of claim 3 , wherein the cancer is multi drug resistant.
11 . The method of claim 3 , wherein the cancer is metastatic.
12 . The method of claim 3 , wherein the cancer is recurrent.
13 . The method of claim 3 , wherein treating comprises inhibiting cancer growth, killing cancer cells, reducing tumor burden, reducing tumor size, improving said subject's quality of life or prolonging said subject's length of life.
14 . The method of claim 3 , wherein the subject is a human.
15 . The method of claim 3 , wherein the subject is a non-human animal.
16 . A pharmaceutical composition comprising a pharmaceutically acceptable amount of the inhibitor according to claim 1 and a pharmaceutically acceptable carrier.
17 . A method of treating breast cancer in a subject in need thereof, comprising administering to the subject, the 17β-HSD7 inhibitor compound of claim 2 .
18 . The method of claim 17 , wherein the cancer is an estrogen-sensitive cancer.
19 . The method of claim 17 , further comprising treating the subject with a secondary cancer therapy.
20 . The method of claim 19 , wherein the secondary cancer therapy is selected from the group consisting of chemotherapy, toxin therapy, radiation therapy, hormone or anti-hormone therapy, surgery, cryotherapy, or immunotherapy.