Inhibitors of multidrug resistance transporter p-glycoprotein

Patent metadata

Field	Value
Publication number	US-11013739-B2
Application number	US-201916675882-A
Country	US
Kind code	B2
Filing date	Nov 6, 2019
Priority date	Jan 15, 2014
Publication date	May 25, 2021
Grant date	May 25, 2021

Abstract

The present disclosure provides a method of treating a subject that is resistant to one or more drugs by identifying a subject having one or more drug resistant cells; administering to the subject a pharmaceutically effective amount of an inhibitor compound, and contacting one or more drug resistant cells with the inhibitor compound to reduce the export of the inhibitor compound from the one or more drug resistant tumor cells and to block the transport of drug(s) from the one or more drug resistant cells.

First claim

What is claimed is:

1. A method of treating a subject having prostate or liver cancer that is resistant to one or more chemotherapeutic drugs comprising the steps of:
identifying a subject having one or more drug resistant prostate or liver cancer cells that express a P-glycoprotein;
administering to the subject a pharmaceutically effective amount of an inhibitor compound having one of the following structural formulas:

 and
contacting one or more drug resistant prostate or liver cancer cells with the inhibitor compound to reduce the drug resistance of the cancer cells.

2. The method of claim 1 , wherein the inhibitor compound interacts with an exporter protein.

3. The method of claim 1 , wherein the inhibitor compound is a P-glycoprotein inhibitor.

4. The method of claim 1 , wherein the inhibitor compound interacts with drug-toxin pumping structures of a P-glycoprotein.

5. The method of claim 1 , wherein the inhibitor compound interacts with ATP binding domain(s) of a P-glycoprotein and the inhibitor compound does not bind to drug binding site(s) on the P-glycoprotein.

6. The method of claim 1 , wherein the inhibitor compound is transported by a P-glycoprotein.

7. The method of claim 1 , wherein the one or more drug resistant prostate or liver cancer cells are one or more multidrug resistant prostate or liver tumor cells.

8. The method of claim 1 , further comprising the step of administering one or more chemotherapeutic agents to the subject.

9. The method of claim 1 , wherein the inhibitor compound is effective for at least one of: increasing the effectiveness of the chemotherapeutic drug to inhibit proliferation, inducing cell death, or indirectly inhibiting development of a tumor by suppressing tumor angiogenesis, reducing the export of the inhibitor compound from the one or more drug resistant tumor cells, to block the transport of chemotherapeutic drug(s) from the one or more drug resistant cancer cells, or increasing an efficacy of one or more chemotherapeutics and/or decreasing toxicity of the chemotherapeutic treatment(s).

10. The method of claim 1 , wherein the inhibitor compound sensitizes or re-sensitizes a prostate or liver cancer cell to a chemotherapeutic agent to which the cancer has become refractory.

11. The method of claim 1 , wherein the inhibitor compound the transport of the one or more chemotherapeutic drug(s) from the one or more prostate or liver cancer cells to sensitization or re-sensitization of the one or more prostate or liver cancer cells to the one or more chemotherapeutic drug(s).

12. The method of claim 1 , wherein the inhibitor compound increases an efficacy of one or more chemotherapeutics and/or decreasing toxicity of one or more chemotherapeutic.

Assignees

• Univ Southern Methodist

Inventors

• Wise John G
• Vogel Pia D
• Brewer Frances K
• Follit Courtney A
• Nanyakkara Amila K
• Lippert Alexander R
• Aljowni Maha Ali

Classifications

• A61K31/352 Primary

  condensed with carbocyclic rings, e.g. methantheline  {(cannabinoids A61K31/658)} · CPC title

• A61K31/5025 Primary

  ortho- or peri-condensed with heterocyclic ring systems · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• A61K31/4545

  containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine · CPC title

• A61K31/4196

  1,2,4-Triazoles · CPC title