MAO inhibitors and their conjugates as therapeutics for the treatment of brain cancer

Patent metadata

Field	Value
Publication number	US-9675620-B2
Application number	US-201514615416-A
Country	US
Kind code	B2
Filing date	Feb 5, 2015
Priority date	Jul 26, 2011
Publication date	Jun 13, 2017
Grant date	Jun 13, 2017

Abstract

A pharmaceutical composition and method for treating brain cancer are provided. The method includes administering to a patient in need thereof an effective amount of one or more compounds that include moclobemide, clorgyline, clorgyline's Near-infra-red dye Monoamine Oxidase Inhibitor (NMI), and MHI 148-clorgyline, and their salt thereof. The composition and method are particularly effective in reducing the size of glioblastomas that are temozolomide (TMZ) resistant.

First claim

The invention claimed is:

1. A method of treating brain cancer, comprising: administering to a patient having brain cancer an effective amount of a monoamine oxidase (MAO) inhibitor, wherein the brain cancer comprises a glioblastoma, and wherein the glioblastoma is a temozolomide resistant glioblastoma.

2. The method of claim 1 , further comprising administering temozolomide in combination with the MAO inhibitor.

3. The method of claim 2 , wherein the temozolomide is administered in combination with the MAO inhibitor.

4. The method of claim 3 , wherein the temozolomide and the MAO inhibitor are administered sequentially.

5. The method of claim 1 , wherein the brain cancer is Glioblastoma multiforme.

6. The method of claim 1 , further comprising administering temozolomide in combination with the MAO inhibitor.

7. The method of claim 1 , wherein the MAO inhibitor is selected from the group consisting of

and salts thereof.

8. The method of claim 1 , wherein the MAO inhibitor is selected from the group consisting of

9. The method of claim 7 , wherein said monoamine oxidase inhibitor is covalently linked to a near infrared dye via a linker.

10. The method of claim 9 , wherein the near infrared dye comprises a polyene functional groups.

11. The method of claim 10 , wherein the near infrared dye is selected from the group consisting of IR-783, IR-780, IR-786 and MHI-148.

12. The method of claim 11 , wherein the MAO inhibitor is selected from the group consisting of NMI, MHI-148-moclobemide, MHI-148-phenelzine, MHI-148-tranylcypromine, MHI-148-pargyline, MHI-148-clorgyline, MHI-148-MAOIs, and near infrared dye-MAOIs (NIR-MAOIs).

13. The method of claim 1 , wherein the MAO inhibitor has the formula:

14. The method of claim 9 , wherein the MAO inhibitor-dye conjugate is selected from the group consisting of

and salts, carboxylic acids or esters thereof.

15. The method of claim 1 , further comprising concurrently or sequentially administering to the patient one or more additional treatments for brain cancer, wherein the one or more additional treatments include surgery, radiation and chemotherapy.

16. A method of treating brain cancer, comprising:
administering to a person in need thereof having a temozolomide-resistant glioblastoma an effective amount of a pharmaceutical composition comprising a salt of

or a carboxylic acid or ester analog thereof.

Assignees

• Univ Southern California

Inventors

• Shih Jean C
• Hofman Florence M
• Chen Thomas C

Classifications

• C12N15/1137

  against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138) · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K49/16

  Antibodies; Immunoglobulins; Fragments thereof · CPC title

• A61K31/381

  having five-membered rings · CPC title

• C12Y104/03004

  Monoamine oxidase (1.4.3.4) · CPC title