Inhibition of focal adhesion kinase for control of scar tissue formation

• US 9,655,967 B2
• Filed: 12/05/2012
• Issued: 05/23/2017
• Est. Priority Date: 12/09/2011
• Status: Active Grant

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford University)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford University)
• Inventors: Wong, Victor W., Gurtner, Geoffrey C., Longaker, Michael T.
• Primary Examiner(s): Gembeh, Shirley V
• Application Number:
  US13/706,186
• Publication Number:
  US 20130165463A1
• Time in Patent Office: 1,630 Days
• Field of Search: 514275
• 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 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

The formation of scars at a wound site is reduced by contacting the wound site with an effective dose of an inhibitor of focal adhesion kinase (FAK) activity or expression. Blockade of FAK is sufficient to prevent mechanical and inflammatory stimuli from activating MCP-1 pathways. In addition to these chemokine-mediated mechanisms, inhibition of FAK may control fibrosis by blocking fibroblast collagen production. Pharmacologic blockade of FAK significantly reduces scar formation in vivo.

Claims

1. A method of reducing scarring during healing of a skin wound, comprising:

administering to a subject with a skin wound a pharmaceutical formulation comprising an effective dose of an FAK inhibitor selected from;

PF-573,228, PF-562,271, FAK Inhibitor 14, a 2,4,DI (hetero-) arylamino (-oxy)-5-substituted pyrimidine, a derivative of a 5-substituted 2,4-diaminopyridine, and a combination thereof;

for a period of time sufficient to reduce scarring as compared to a healed wound of an untreated subject.

2. The method of claim 1, wherein the FAK inhibitor is selected from:

PF-573,228 and FAK Inhibitor 14.

3. A method of reducing scarring during healing of a skin wound, comprising:

administering to a human subject with a skin wound a pharmaceutical formulation comprising;

(i) an effective dose of an FAK inhibitor selected from;

PF-573,228, FAK Inhibitor 14, and a combination thereof; and

(ii) one or both of an antibiotic and a non-steroidal anti-inflammatory drug,

for a period of time sufficient to reduce scarring by at least about 25% relative to a healed wound of an untreated subject.