Method of reversing epithelial mesenchymal transition

• US 20060234911A1
• Filed: 03/24/2006
• Published: 10/19/2006
• Est. Priority Date: 03/24/2005
• Status: Abandoned Application

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Das, Shreyasi, Hoffmann, F. Michael
• Application Number:
  US11/388,433
• Publication Number:
  US 20060234911A1
• Time in Patent Office: Days
• US Class Current: 514/183
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 38/1833 Hepatocyte growth factor; Scatter factor; Tumor cytotoxic factor II
• CPC Class Codes: A61K 38/1875 Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor

Abstract

A method of reversing epithelial mesenchymal transition, comprising the step of treating a fibrotic disease patient or cancer disease patient with an amount of kinase inhibitor capable of reversing EMT, wherein the kinase inhibitor comprises a TGF-βI kinase inhibitor and a Rho kinase inhibitor or a TGF-βI inhibitor and a p38 MAPK inhibitor is disclosed.

Claims

1. A method of reversing epithelial mesenchymal transition, comprising the step of treating a fibrotic disease patient or cancer disease patient with an amount of kinase inhibitor capable of reversing EMT, wherein the kinase inhibitor comprises a TGF-β

I kinase inhibitor and a Rho kinase inhibitor or a TGF-β

I inhibitor and a p38 MAPK inhibitor.

2. The method of claim 1 wherein the administration of the inhibitors is simultaneous.

3. The method of claim 1 wherein the TGF-β

I inhibitor is SB431542.

4. The method of claim 1 wherein the TGF-β

I inhibitor is selected from the group consisting of SB431542, SD-208, SB-525334, SM16, and LY2157299.

5. The method of claim 1 wherein the Rho kinase inhibitor is Y27632.

6. The method of claim 1 wherein the Rho kinase inhibitor is Y27632 and the TGF-β

I inhibitor is SB431542.

7. The method of claim 1 wherein the p38 MAPK inhibitor is selected from the group consisting of SB203580 and SB202190.

8. The method of claim 1 wherein the Rho kinase inhibitor is a statin.

9. The method of claim 1 wherein the disease is selected from the group consisting of diabetic nephropathy, liver cirrhosis, scleroderma, scarring, keloids and adhesions.

10. The method of claim 1 wherein the inhibitors are administered via the group consisting of tablets, coated tablets, capsules, pills, aqueous solutions, suspensions, emulsions, sterile injectable solutions, nonaqueous emulsions, suspensions and solutions, sprays and forms with protracted release of active compound.

11. A pharmaceutical composition comprising an amount of kinase inhibitor capable of reversing EMT, wherein the kinase inhibitor comprises a TGF-β

I kinase inhibitor and a Rho kinase inhibitor or a TGF-β

I inhibitor and a p38 MAPK inhibitor.

12. The composition of claim 11 wherein the composition is in the form of tablets, coated tablets, capsules, pills, aqueous solutions, suspensions, emulsions, sterile injectable solutions, nonaqueous emulsions, suspensions and solutions, sprays and forms with protracted release of active compound.

13. The composition of claim 11 wherein the TGF-β

I inhibitor is selected from the group consisting of SB431542, SD-208, SB-525334, SM16, and LY2157299.

14. The composition of claim 11 wherein the Rho kinase inhibitor is Y27632.