# US 10,478,437 B2 · Combination therapy to enhance the anticancer efficacy of platinum drugs

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- Number: US 10,478,437 B2
- Document ID: US10478437B2
- Status: Granted
- Kind: B2
- Application number: 15/380,776
- Filed: 2016-12-15
- Published: 2017-04-06
- Granted: 2019-11-19
- Earliest claimed: 2014-06-18
- Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Applicants: University of Pittsburgh-of the Commonwealth System of Higher Education
- Inventors: Wei Qian; Peter Wipf; Bennett Van Houten
- Web page: https://patentgrep.com/patent/US10478437B2

## CPC

- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 31/282: Platinum compounds
- A61K 31/428: condensed with carbocyclic rings
- A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof
- A61K 31/4436: containing a heterocyclic ring having sulfur as a ring hetero atom
- A61K 31/513: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
- A61K 33/243: Platinum; Compounds thereof
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to compositions and methods for reducing cell proliferation and/or promoting cell death. It is based, at least in part, on the discovery that in platinum drug-resistant cell lines, certain compounds, together with a second antiproliferative agent (e.g., cisplatin), act synergistically to promote apoptosis. Accordingly, the present invention provides for novel anticancer strategies.

## Claims

### Claim 1

A method for reducing cancer cell proliferation and/or promoting cancer cell death by administering, to a cancer cell, an effective amount of a compound having a formula selected from the group consisting of Formula I:
wherein G is C; Q is C; and R is selected from H, a substituted or unsubstituted alkyl, a fluorinated or partially fluorinated alkyl, a halogen, cyano, azido, hydroxyl, a substituted or unsubstituted sulfonyl;

### Claim 2 (depends on 1)

The method of claim 1, further comprising administering, to the cancer cell, an effective amount of a second antiproliferative agent.

### Claim 3 (depends on 2)

The method of claim 2, wherein the second antiproliferative agent is a platinum compound.

### Claim 4 (depends on 3)

The method of claim 3, wherein the platinum compound is cisplatin.

### Claim 5 (depends on 3)

The method of claim 3, wherein the platinum compound is carboplatin.

### Claim 6

A method for reducing cancer cell proliferation and/or promoting cancer cell death in a subject in need of such treatment comprising administering, to the subject, an effective amount of a compound having a formula selected from the group consisting of Formula I:
wherein G is C; Q is C; and R is selected from H, a substituted or unsubstituted alkyl, a fluorinated or partially fluorinated alkyl, a halogen, cyano, azido, hydroxyl, a substituted or unsubstituted sulfonyl;

### Claim 7 (depends on 6)

The method of claim 6, wherein the compound is a compound having the Formula VII

### Claim 8 (depends on 6)

The method of claim 6, wherein the compound is a compound having the Formula II

### Claim 9 (depends on 6)

The method of claim 6, wherein the compound is a compound having the Formula IV

### Claim 10 (depends on 6)

The method of claim 6, wherein the compound is a compound having the Formula V

### Claim 11 (depends on 6)

The method of claim 6, wherein the compound is a compound having the Formula VIII

### Claim 12 (depends on 6)

The method of claim 6, wherein the cancer is selected from the group consisting of breast cancer, lung cancer, ovarian cancer, glioblastoma, squamous cell carcinoma of the head and neck, melanoma and colon cancer.

### Claim 13 (depends on 6)

The method of claim 6, further comprising administering, to the subject, an effective amount of a second antiproliferative agent.

### Claim 14 (depends on 13)

The method of claim 13, wherein the second antiproliferative agent is a platinum compound.

### Claim 15 (depends on 14)

The method of claim 14, wherein the platinum compound is cisplatin.

### Claim 16 (depends on 14)

The method of claim 14, wherein the platinum compound is carboplatin.

### Claim 17 (depends on 6)

The method of claim 6, wherein the cancer is breast cancer.

### Claim 18 (depends on 6)

The method of claim 6, wherein the cancer is lung cancer.

### Claim 19 (depends on 6)

The method of claim 6, wherein the cancer is ovarian cancer.

### Claim 20 (depends on 6)

The method of claim 6, wherein the cancer is glioblastoma.

### Claim 21 (depends on 6)

The method of claim 6, wherein the cancer is squamous cell carcinoma of the head and neck.

### Claim 22 (depends on 6)

The method of claim 6, wherein the cancer is melanoma.

### Claim 23 (depends on 6)

The method of claim 6, wherein the cancer is colon cancer.

### Claim 24

A pharmaceutical formulation comprising an effective amount of a compound for reducing cancer cell proliferation and/or promoting cancer cell death, having a formula selected from the group consisting of Formula I:
wherein G is C; Q is C; and R is selected from H, a substituted or unsubstituted alkyl, a fluorinated or partially fluorinated alkyl, a halogen, cyano, azido, hydroxyl, a substituted or unsubstituted sulfonyl;
and a pharmaceutically acceptable buffer.

### Claim 25 (depends on 24)

The pharmaceutical formulation of claim 24, further comprising an effective amount of a second antiproliferative agent compound.

### Claim 26 (depends on 25)

The pharmaceutical formulation of claim 25, wherein the second antiproliferative agent is a platinum compound.

### Claim 27 (depends on 26)

The pharmaceutical formulation of claim 26, wherein the platinum compound is cisplatin.

### Claim 28 (depends on 26)

The pharmaceutical formulation of claim 26, wherein the platinum compound is carboplatin.

### Claim 29 (depends on 24)

The pharmaceutical formulation of claim 24, wherein the compound is a compound having the Formula VII

### Claim 30

A kit comprising a container comprising an effective amount of a compound for reducing cancer cell proliferation and/or promoting cancer cell death, having a formula selected from the group consisting of Formula I:
wherein G is C; Q is C; and R is selected from H, a substituted or unsubstituted alkyl, a fluorinated or partially fluorinated alkyl, a halogen, cyano, azido, hydroxyl, a substituted or unsubstituted sulfonyl;
and a pharmaceutically acceptable buffer.

### Claim 31 (depends on 30)

The kit of claim 30, further comprising an effective amount of a second antiproliferative agent compound.

### Claim 32 (depends on 31)

The kit of claim 31, wherein the second antiproliferative agent is a platinum compound.

### Claim 33 (depends on 32)

The kit of claim 32, wherein the platinum compound is cisplatin.

### Claim 34 (depends on 32)

The kit of claim 32, wherein the platinum compound is carboplatin.

### Claim 35 (depends on 30)

The kit of claim 30, wherein the compound is a compound having the Formula VII