Potent anticancer activity via dual compound activation

Patent metadata

Field	Value
Publication number	US-9592229-B2
Application number	US-201314382546-A
Country	US
Kind code	B2
Filing date	Mar 4, 2013
Priority date	Mar 2, 2012
Publication date	Mar 14, 2017
Grant date	Mar 14, 2017

Abstract

The invention provides compositions and methods for the induction of cell death, for example, cancer cell death. Combinations of compounds and related methods the use are disclosed, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells. The disclosed drug combinations can have lower neurotoxicity effects than other compounds and combinations of compounds.

First claim

What is claimed is:

1. A composition comprising (a) a compound of Formula (I):

wherein R is H or Me;
(b) the compound PAC-1:

and (c) a pharmaceutically acceptable diluent, excipient, or carrier.

2. The composition of claim 1 wherein R of Formula (I) is H.

3. The composition of claim 1 wherein R of Formula (I) is Me.

4. The composition of claim 1 wherein the carrier comprises water and optionally a buffer, a cyclodextrin, or a combination thereof.

5. The composition of claim 4 wherein the carrier comprises a cyclodextrin wherein the cyclodextrin is 2-hydroxypropyl-β-cyclodextrin.

6. A method of inhibiting the growth or proliferation of cancer cells comprising contacting cancer cells with an effective amount of a composition of claim 1 , thereby inhibiting the growth or proliferation of the cancer cells.

7. The method of claim 6 wherein the cancer cells are cells of anal cancer, bladder cancer, breast cancer, cervical cancer, colorectal cancer, gastric cancer, head and neck cancer, leukemia, lung cancer Hodgkin's lymphoma, Non-Hodgkin's lymphoma, malignant lymphoma, neuroblastomas, ophthalmic cancer, osteogenic carcinomas, ovarian cancer, prostate cancer, renal cancer melanoma, soft tissue sarcomas, thyroid cancer, or Wilms' tumor.

8. The method of claim 6 wherein the cancer cells are breast cancer cells, leukemia cells, or lymphoma cells.

9. A method of activating procaspase-3 to caspase-3 comprising contacting the procaspase-3 with a composition of claim 1 .

10. The method of claim 9 wherein the contacting is in vitro.

11. The method of claim 9 wherein the contacting is in vivo.

12. A method of potentiating the activity of a compound of Formula (I):

wherein R is H or Me;
comprising contacting a cancer cell with a combination of the compound of Formula I and an effective activating amount of PAC-1:

wherein the PAC-1 potentiates the activity of the compound of Formula (I) toward the cancer cell.

13. A method of inducing apoptosis in a cancer cell comprising contacting the cancer cell with an effective amount of a compound of Formula (I):

wherein R is H or Me;
and an effective amount of the compound PAC-1:

wherein apoptosis is thereby induced in the cancer cell.

14. The method of claim 13 wherein the cancer cell is contacted with the compound of Formula (I) and the PAC-1 concurrently.

15. The method of claim 13 wherein the cancer cell is contacted with the compound of Formula (I) prior to contacting the cancer cell with PAC-1.

16. The method of claim 13 wherein the cancer cell is contacted with PAC-1 prior to contacting the cancer cell with the compound of Formula (I).

17. A method of inhibiting cancer, arresting cancer, relieving cancer, reversing the progression of cancer, reversing the severity of cancer, and/or therapeutically treating cancer, in a patient in need thereof comprising administering to the patient, concurrently or sequentially, a therapeutically effective amount of a compound of Formula (I):

wherein R is H or Me;
and an effective amount of the compound PAC-1:

wherein the cancer is breast cancer, leukemia, or lymphoma.

18. The method of claim 17 wherein the compound of Formula (I) and the compound PAC-1 are administered concurrently.

19. The method of claim 17 wherein the compound of Formula (I) and the compound PAC-1 are administered sequentially.

20. The method of claim 19 wherein the compound of Formula (I) is administered before the compound PAC-1.

21. The method of claim 19 wherein the compound of Formula (I) is administered after the compound PAC-1.

Assignees

• Univ Illinois
• Vanquish Oncology Inc

Inventors

• Hergenrother Paul J
• Botham Rachel C
• Fan Timothy M
• Gilbert Mark J
• Handley Michael K
• Tarasow Theodore M

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K9/4858

  Organic compounds · CPC title

• A61K9/0019

  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 title