Compositions and methods for treating and preventing cancer using analogs of vitamin D

• US 20050059641A1
• Filed: 06/17/2004
• Published: 03/17/2005
• Est. Priority Date: 06/17/2003
• Status: Abandoned Application

• Current Assignee: Trustees of Boston University
• Original Assignee: Aphios Corporation
• Inventors: Ray, Rahul, Swamy, Narashima
• Application Number:
  US10/870,122
• Publication Number:
  US 20050059641A1
• Time in Patent Office: Days
• US Class Current: 514/167
• 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 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61K 31/593 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07C 401/00 Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation

Abstract

Disclosed are compositions and methods used to treat and/or prevent cancer and metabolic diseases, such as psoriasis. In one aspect, the present invention pertains to the use of cross-linking analogs of vitamin D and its metabolites employed for the treatment of prostate cancer.

Claims

1. A composition comprising an analog of 1,25(OH)₂D₃, wherein said analog is alkylated or acylated.

2. The composition of claim 1, wherein said analog cross links said 1,25(OH)₂D₃ to a hormone-binding pocket of VDR.

3. The composition of claim 1, wherein said analog is selected from the group consisting of 1,25(OH)₂D₃-3-BE, 25(OH)₂D₃-3-BE and derivatives thereof.

4. A method of treating and/or preventing cancer in a subject by administering to said subject an effective amount of an analog of 1,25(OH)₂D₃, wherein said analog is alkylated or acylated.

5. The method of claim 4, wherein said cancer is prostate cancer.

6. The method of claim 4, wherein said analog cross links said 1,25(OH)₂D₃ to a hormone-binding pocket of VDR.

7. The method of claim 4, wherein said analog is selected from the group consisting of 1,25(OH)₂D₃-3-BE, 25(OH)₂D₃-3-BE and derivatives thereof.

8. A method of treating and/or preventing cancer in a subject by administering a combination pharmaceutical formulation comprising an effective amount of an analog of 1,25(OH)₂D₃ and an effective amount of a known oncolytic agent, wherein said analog is alkylated of acylated.

9. The method of claim 8, wherein said cancer is prostate cancer.

10. The method of claim 8, wherein said analog cross links said 1,25(OH)₂D₃ to a hormone-binding pocket of VDR.

11. The method of claim 8, wherein said analog is selected from the group consisting of 1,25(OH)₂D₃-3-BE, 25(OH)₂D₃-3-BE and derivatives thereof.

12. The method of claim 8, wherein said oncolytic agent is is selected from the group consisting of paclitaxel, 5-FU, 5-FUdR, methotrexate, ara-C, 6-mercaptopurine, 6-thioguanine, hydroxyurea, mechlorethamine, phenylalanine mustard, chlorambucil, ethylenimines, methyl melamines, carmustine, lomustine, streptozocin, Cisplatin, Carboplatin, dacarbazine, procarbazine, doxorubicin, daunorubicin, mitomycin C, plycamycin, cyclophosphamide, melphalan, chlorambucil, carmustine, thiotepa, busulfan, prednisone, prednisolone, triamcinolone, and derivatives thereof.