Methods for treating cancer with RORγ inhibitors

Patent metadata

Field	Value
Publication number	US-10959984-B2
Application number	US-201715701122-A
Country	US
Kind code	B2
Filing date	Sep 11, 2017
Priority date	Mar 12, 2015
Publication date	Mar 30, 2021
Grant date	Mar 30, 2021

Abstract

The present invention provides compositions, methods, and kits comprising one or more RORγ inhibitors, alone or in combination with one or more anticancer drugs, such as an anti-androgen drug, that are useful for treating cancer, e.g., prostate cancer, such as castration-resistant prostate cancer (CRPC), and numerous other types of cancer including lung cancer, breast cancer, liver cancer, ovarian cancer, endometrial cancer, bladder cancer, colon cancer, lymphoma, and glioma.

First claim

What is claimed is:

1. A method for treating a cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of a retinoic acid receptor-related orphan receptor γ (RORγ) inhibitor,
wherein the cancer is selected from the group consisting of prostate cancer, breast cancer, lung cancer, ovarian cancer, bladder cancer, endometrial cancer, liver cancer, glioblastoma, B-cell lymphoma, and colon cancer, wherein the cancer is resistant to an anticancer drug and
wherein the RORγ inhibitor selectively binds to RORγ and is selected from the group consisting of 2-Fluoro-4′-[[4-(4-pyridinylmethyl)-1-piperazinyl]methyl]-a, a-bis(trifluoromethyl) -[1,1′-biphenyl]-4-methanol (SR2211), N-(3,5-Dichloro-4-(2-(trifluoromethoxy)phenyl)phenyl) -2-(4-ethylsulfonylphenyl)acetamide (GSK805), analogs thereof, and combinations thereof.

2. The method of claim 1 , wherein the anticancer drug is a chemotherapeutic agent, wherein the chemotherapeutic agent is tamoxifen, a taxane, an anthracenedione, or combinations thereof.

3. The method of claim 2 , wherein the taxane is selected from the group consisting of paclitaxel, docetaxel, cabazitaxel, hongdoushan A, hongdoushan B, hongdoushan C, baccatin I, baccatin II, 10-deacetylbaccatin, and combinations thereof.

4. The method of claim 1 , wherein the prostate cancer is a castration-resistant prostate cancer.

5. The method of claim 1 , wherein the lung cancer is a non-small-cell lung cancer (NSCLC), K-Ras mutant lung cancer, BRAF mutant lung cancer, EGFR mutant lung cancer, tyrosine kinase inhibitor-resistant lung cancer, or small cell lung cancer (SCLC).

6. The method of claim 1 , wherein the breast cancer is a triple-negative breast cancer (TNBC), tamoxifen-resistant breast cancer, radiation-resistant breast cancer, HER2-positive breast cancer, or ER-positive breast cancer.

7. The method of claim 1 , wherein the subject is a human in need of cancer treatment.

8. The method of claim 1 , wherein the method further comprises administering to the subject an effective amount of the anticancer drug.

9. The method of claim 8 , wherein the RORγ inhibitor enhances the therapeutic effect of the anticancer drug.

10. The method of claim 9 , wherein the RORγ inhibitor reverses or reduces cancer cell resistance to the anticancer drug and/or sensitizes cancer cells to the anticancer drug.

11. The method of claim 8 , wherein the anticancer drug is a chemotherapeutic agent, wherein the chemotherapeutic agent is tamoxifen, a taxane, an anthracenedione, or combinations thereof.

12. The method of claim 11 , wherein the taxane is selected from the group consisting of paclitaxel, docetaxel, cabazitaxel, hongdoushan A, hongdoushan B, hongdoushan C, baccatin I, baccatin II, 10-deacetylbaccatin, and combinations thereof.

13. The method of claim 8 , wherein the subject is a human in need of cancer treatment.

14. The method of claim 1 , wherein the anticancer drug is an endocrine therapy, wherein the endocrine therapy is selected from the group consisting of tamoxifen, raloxifene, an aromatase inhibitor, megestrol acetate, lasofoxifene, bazedoxifene, bazedoxifene/conjugated estrogens, and combinations thereof.

15. The method of claim 8 , wherein the anticancer drug is an endocrine therapy, wherein the endocrine therapy is selected from the group consisting of tamoxifen, raloxifene, an aromatase inhibitor, megestrol acetate, lasofoxifene, bazedoxifene, bazedoxifene/conjugated estrogens, and combinations thereof.

16. The method of claim 1 , wherein the RORγ inhibitor selectively binds to RORγ relative to RORα and/or RORβ.

17. The method of claim 8 , wherein the RORγ inhibitor selectively binds to RORγ relative to RORα and/or RORβ.

18. The method of claim 1 , wherein the RORγ inhibitor is SR2211.

19. The method of claim 1 , wherein the RORγ inhibitor is GSK805.

Assignees

• Univ California

Inventors

• Chen Hongwu
• Zou June X
• Wang Junjian

Classifications

• A61K31/185

  Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids (hydroxamic acids A61K31/16; peroxy acids A61K31/327) · CPC title

• C12N15/1138

  against receptors or cell surface proteins · CPC title

• C07D419/12

  linked by a chain containing hetero atoms as chain links · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title