Cell migration inhibiting compositions and methods and compositions for treating cancer

• US 7,700,615 B2
• Filed: 02/01/2006
• Issued: 04/20/2010
• Est. Priority Date: 06/04/2002
• Status: Expired due to Fees

• Current Assignee: Avolix Pharmaceuticals Incorporated
• Original Assignee: Avolix Pharmaceuticals Incorporated
• Inventors: Edwards, David L., Beaudry, Christian, Berens, Michael E.
• Primary Examiner(s): Marschel; Ardin
• Assistant Examiner(s): Vakili; Zohreh
• Application Number:
  US11/345,132
• Publication Number:
  US 20060128742A1
• Time in Patent Office: 1,539 Days
• Field of Search: 514/294, 514/741, 514/740, 514/751
• US Class Current: 514/294
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/549 having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: G01N 2500/10 involving cells
• CPC Class Codes: G01N 33/5011 for testing antineoplastic activity

Abstract

Methods for treating an individual having cancer are provided. The method may include administering a cell migration inhibitor and a chemotherapeutic agent to the individual to inhibit migration of cancer cell. Inhibiting cell migration may increase cell division. In this manner, the cell migration inhibitor and the chemotherapeutic agent in combination may have increased efficacy compared to the chemotherapeutic agent alone due to the increased cell division. The cell migration inhibitor may include any of the inhibitors described herein. For example, the cell migration inhibitor may be an organic molecule having a molecular weight of less than about 700, a monoclonal antibody, or a natural product.

Claims

1. A pharmaceutical composition, comprising a cell migration inhibitor and a chemotherapeutic agent, wherein the inhibitor is 1-(4-chloro-benzoyl)-2-(3,4-dimethoxy-phenyl)-1,2-dihydro-3aH-pyrrolo[1,2-a]quinoline-3,3-dicarbonitrile.

2. The composition of claim 1, wherein the chemotherapeutic agent is selected from the group consisting of an alkylating agent, an antitumor antibiotic, an antimetabolite, an antimicrotubule agent, a spindle-tubule inhibitor, a topoisomerase inhibitor, a hormonal agent, a biological agent, and a granulocyte-colony stimulating factor.

6. The composition of claim 1, wherein the chemotherapeutic agent is 1,3-bis(2-chloroethyl)-1-nitrosourea.

7. The composition of claim 1, wherein the chemotherapeutic agent is paclitaxel.

8. The composition of claim 1, wherein the chemotherapeutic agent is fluorouracil.

9. The composition of claim 1, wherein the chemotherapeutic agent is cytarabine.

11. The composition of claim 1, wherein the chemotherapeutic agent is gemcytabine.

3. A method for treating an individual having cancer, comprising administering a cell migration inhibitor and a chemotherapeutic agent to the individual, wherein the inhibitor is 1-(4-chloro-benzoyl)-2-(3,4-dimethoxy-phenyl)-1,2-dihydro-3aH-pyrrolo[1,2-a]quinoline-3,3-dicarbonitrile.

10. The method of claim 3, wherein the chemotherapeutic agent is selected from the group consisting of alkylating agent, an antitumor antibiotic, an antimetabolite, an antimicrotubule agent, a spindle-tubule inhibitor, a topoisomerase inhibitor, a hormonal agent, a biological agent, and a granulocyte-colony stimulating factor.

4. A pharmaceutical composition, comprising a cell migration inhibitor and a chemotherapeutic agent, wherein the cell migration inhibitor is 1-(4-chloro-benzoyl)-2-(3,4-dimethoxy-phenyl)-1,2-dihydro-3aH-pyrrolo[1,2-a]quinoline-3,3-dicarbonitrile, wherein the chemotherapeutic agent is gemcytabine, and wherein the composition exhibits synergistic killing of pancreatic cancer cells.

5. A method for treating an individual having pancreatic cancer, comprising administering a cell migration inhibitor and a chemotherapeutic agent to the individual, wherein the cell migration inhibitor is 1-(4-chloro-benzoyl)-2-(3,4-dimethoxy-phenyl)-1,2-dihydro-3aH-pyrrolo[1,2-a]quinoline-3,3-dicarbonitrile, wherein the chemotherapeutic agent is gemcytabine.