Metal salts and uses thereof
The present invention relates to metal salts of 2-[3-[(3R)-3-[[2-chloro-3-(trifluoromethyl)phenyl]methyl-(2,2-diphenylethyl)amino]butoxy]phenyl]acetic acid which exhibit improved physical properties and stability. The invention also relates to pharmaceutical compositions including an effective amount of the metal salts, as well as methods of treating cancer including administration of a pharmaceutical composition including a salt of the invention to a subject in need thereof.
1. A method of treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of a zinc salt of 2-[3-[(3R)-3-[[2-chloro-3-(trifluoromethyl)phenyl]methyl-(2,2-diphenylethyl)amino]butoxy]phenyl]acetic acid (Compound 1), wherein the zinc salt is a 2:1 (Compound 1:zinc) salt and wherein the cancer is selected from the group consisting of breast cancer, endometrial cancer, colon cancer, renal cell cancer, lung cancer, hepatocellular carcinoma, gastric cancer, ovarian cancer, pancreatic cancer, esophageal cancer, prostate cancer, sarcoma, bladder cancer, head and neck cancer, glioblastoma, diffuse large B-cell lymphoma, leukemia, and melanoma.
2. The method of claim 1 , wherein the method comprises orally administering the zinc salt formulated as a pharmaceutical composition for oral administration comprising (i) the zinc salt of 2-[3-[(3R)-3-[[2-chloro-3-(trifluoromethyl)phenyl]methyl-(2,2-diphenylethyl)amino]butoxy]phenyl]acetic acid (Compound 1), wherein the zinc salt is a 2:1 (Compound 1:zinc) salt, and (ii) a pharmaceutically acceptable excipient.
3. The method of claim 2 , wherein the pharmaceutical composition is in the form of an emulsion, an aqueous suspension, a dispersion, or a solution.
4. The method of claim 3 , wherein the pharmaceutical composition is in unit dosage form.
5. The method of claim 4 , wherein the pharmaceutical composition is a unit dosage form comprising a capsule or a tablet.
6. The method of claim 4 , wherein the pharmaceutical composition is a unit dosage form comprising a solution of the zinc salt.
7. The method of claim 1 , wherein the cancer is metastatic cancer.
8. The method of claim 7 , wherein the effective amount comprises an amount effective to suppress metastatic colonization of said cancer.
9. The method of claim 1 , wherein the subject has a cancer that has failed to respond to a previously administered immunotherapy.
10. The method of claim 1 , wherein the subject has a cancer resistant to an immunotherapy.