# US 10,369,127 B2 · Method for inhibiting the expression of ABC transporter protein

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- Number: US 10,369,127 B2
- Document ID: US10369127B2
- Status: Granted
- Kind: B2
- Application number: 15/632,738
- Filed: 2017-06-26
- Published: 2018-02-22
- Granted: 2019-08-06
- Earliest claimed: 2016-08-22
- Assignees: Macau University of Science and Technology
- Applicants: Macau University of Science and Technology
- Inventors: Kam Wai Wong; Yuen Kwan Law; Man Chung Wong
- Web page: https://patentgrep.com/patent/US10369127B2

## CPC

- A61K 31/28: Compounds containing heavy metals
- A61K 31/555: containing heavy metals, e.g. hemin, hematin, melarsoprol
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

A method for inhibiting the expression and/or functional activity of an ABC transporter protein in a subject suffering from a disorder associated with an overexpression of the ABC transporter protein includes administrating a cobalt-polypyridyl complex to the subject. A method for inhibiting the expression and/or functional activity of an ABC transporter in cells includes contacting the cells with an effective amount of the cobalt-polypyridyl complex.

## Claims

### Claim 1

A method for inhibiting the expression and/or functional activity of an ABC transporter protein in a subject suffering from a disorder associated with an overexpression of the ABC transporter protein, comprising the step of administering an effective amount of a cobalt-polypyridyl complex of Formula (II) to the subject:
wherein R1 and R2 are identical and selected from, —CH3, —C9H19 or —OCH3; wherein n is 2 or 3; and wherein the disorder is selected from the group consisting of breast cancer, lung cancer, and colon cancer.

### Claim 2 (depends on 1)

The method of claim 1, wherein the ABC transporter protein is P-glycoprotein.

### Claim 3 (depends on 1)

The method of claim 1, wherein the disorder is multidrug-resistant cancer.

### Claim 4 (depends on 3)

The method of claim 3, wherein the subject is a human and the multidrug-resistant cancer is ABC-protein-dependent against at least taxol.

### Claim 5 (depends on 1)

The method of claim 1, wherein the subject is a human.

### Claim 6 (depends on 1)

The method of claim 1, wherein the cobalt-polypyridyl complex comprises a structure selected from Formula (III), Formula (IV) or Formula (V):

### Claim 7 (depends on 1)

The method of claim 1, wherein the cobalt-polypyridyl complex comprises a structure of Formula (IV):

### Claim 8 (depends on 1)

The method of claim 1, wherein the cobalt-polypyridyl complex is administered in combination with:
(ii) an effective amount of at least one chemotherapeutic compound, which chemotherapeutic compound is a compound selected from the group consisting of a topoisomerase-II inhibitor, an anthracycline, a coordination complex of platinum, a taxane, a protein kinase inhibitor, a vinca alkaloid or derivative thereof, a topoisomerase-I inhibitor and a nucleotide analog or precursor analog;
(ii) radiotherapy, and/or
(iii) immunotherapy.

### Claim 9

A method for inhibiting the expression and/or functional activity of an ABC transporter protein in cells by contacting the cells with an effective amount of a cobalt-polypyridyl complex, wherein the cobalt-polypyridyl complex comprises a structure of Formula (II):
wherein R1 and R2 are identical and selected, —CH3, —C9H19 or —OCH3; wherein n is 2 or 3, and wherein the cells are cancer cells and are selected from the group consisting of breast cancer cells, lung cancer cells, and colon cancer cells.

### Claim 10 (depends on 9)

The method of claim 9, wherein the ABC transporter protein is P-glycoprotein.

### Claim 11 (depends on 9)

The method of claim 9, wherein the cells are contacted with of from about 0.5 μM to about 10 μM of said cobalt-polypyridyl complex.

### Claim 12 (depends on 9)

The method of claim 9, wherein the cells are multidrug-resistant cells with an overexpression of the ABC transporter protein.

### Claim 13 (depends on 9)

The method of claim 9, wherein the cancer cells are multidrug-resistant cancer cells against at least taxol.

### Claim 14 (depends on 9)

The method of claim 9, wherein the cobalt-polypyridyl complex comprises a structure selected from Formula (III), Formula (IV) or Formula (V):

### Claim 15 (depends on 9)

The method of claim 9, wherein the cobalt-polypyridyl complex comprises a structure of Formula (IV):