Method of treating androgen independent prostate cancer

• US 9,040,574 B2
• Filed: 09/20/2012
• Issued: 05/26/2015
• Est. Priority Date: 12/13/2001
• Status: Expired due to Fees

• Current Assignee: Natrogen Therapeutics International, Inc.
• Original Assignee: Natrogen Therapeutics International, Inc.
• Inventors: Wang, Longgui, Mencher, Simon K., McCarron, James P. Jr.
• Primary Examiner(s): West, Theodore R
• Application Number:
  US13/623,861
• Publication Number:
  US 20130022609A1
• Time in Patent Office: 978 Days
• Field of Search: None
• US Class Current: 514/418
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/7056 containing five-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/2004 Excipients; Inactive ingredients
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis

Abstract

The present invention is directed to a method treating prostate cancer. The method comprises administering to a patient in need thereof at least one compound selected from N-methyl-Δ3,3′-dihydroindole-2,2′ diketone; N-1-(β-D-O-triacetyl-xylopranosyl)-Δ3,3′-dihydroindole-2,2′ diketone; and N-1-(β-D-O-triacetyl-xylopranosyl)-N′-methyl-Δ3,3′-dihydroindole-2,2′ diketone. Preferably the compound is in an amount sufficient to inhibit growth, invasion, and/or metastasis of prostate cancer cells.

Claims

1. A method of treating advanced stage prostate cancer, the method comprising administering a compound to a patient in need thereof, wherein the prostate cancer is hormone refractory and/or metastatic and the compound is selected from the group consisting of:

2. The method of claim 1, wherein the prostate cancer is androgen independent and metastatic prostate cancer and the compound is administered in a pharmaceutical composition comprising a pharmaceutical acceptable carrier.

3. The method of claim 1, wherein the compound is in an amount to induce apoptosis of androgen independent cancer cells.

4. The method of claim 1, wherein the patient is human.

5. The method of claim 4, wherein the compound is in an amount sufficient to inhibit at least 30% of invasive cells.

6. The method of claim 5, wherein at least 60% of the invasive cells are inhibited.

7. The method of claim 1, wherein the compound is administered in combination with paclitaxel or paclitaxel derivatives.

8. The method of claim 1, wherein the compound is administered in combination with dexamethasone.

9. The method of claim 1, wherein the compound is administered in combination with a chemotherapeutic agent, a protein kinase inhibitor, a topoisomerase inhibitor, a mitotic kinesin inhibitor, a histone deacetylase inhibitor, a mTOR inhibitor, a growth factor inhibitor, a growth factor receptor inhibitor, a transcriptional factor inhibitor, an anticancer monoclonal antibody, and/or glucocorticoid hormones.

10. The method of claim 9, wherein the chemotherapeutic agent is selected from the group consisting of:

an alkylating agents, anti-metabolitic agents, antibiotics, anti-tubule agents, and anti-hormonal agents.

11. The method of claim 9, wherein the protein kinase inhibitor inhibits at least one of the following:

cyclin-dependent kinases, tyrosine kinases, phosphoinositide 3-kinase PI3K/AKT, protein kinase C, casein kinases, MAP kinases, or Src kinases.

12. The method of claim 1, wherein the compound is administered orally.

13. The method of claim 1, wherein the compound is administered parenterally.

14. The method of claim 13, wherein the compound is administered subcutaneously, intravenously, intramuscularly, or intra-arterially.

15. The method of claim 14, wherein the compound is administered to a human patient, in an amount of about 0.5 mg to 5 mg per kilogram of body weight.

16. The method of claim 1, wherein compound is in a dosage unit forms containing between from about 10 mg to about 240 mg of the compound per day.

17. A method of treating advanced stage prostate cancer, the method comprising administering to a patient having hormone refractory and/or metastatic prostate cancer a compound selected from the group consisting of:

N-methyl-Δ

3,3′

-dihydroindole-2,2′

diketone;

N-1-(β

-D-O-triacetyl-xylopranosyl)-Δ

3,3′

-dihydroindole-2,2′

diketone;

or N-1-(β

-D-O-triacetyl-xylopranosyl)-N′

-methyl-Δ

3,3′

-dihydroindole-2,2′

diketone, wherein the compound is in an amount sufficient to inhibit growth, invasion, and/or metastasis of prostate cancer cells.

18. The method of claim 17, wherein the compound is N-methyl-Δ

3,3′

-dihydroindole-2,2′

diketone.

19. The method of claim 18, wherein the compound is N-1-(β

-D-O-triacetyl-xylopranosyl)-Δ

3,3′

-dihydroindole-2,2′

diketone.

20. The method of claim 18, wherein the compound is N-1-(β

-D-O-triacetyl-xylopranosyl)-N′

-methyl-Δ

3,3′

-dihydroindole-2,2′

diketone.