Angio-inhibitory Peptides Derived from Human TIMP-2

Background:
The National Cancer Institute (NCI) is currently seeking cooperative partners to work with investigators in the Center for Cancer Research (CCR) to exploit, for drug development and clinical testing, novel TIMP-2 peptide-based inhibitors of angiogenesis. Potential application areas include the therapeutic use of novel inhibitors of angiogenesis based on MMP-independent TIMP-2 anti-angiogenesis function.

Technology:
Recent findings made at the National Cancer Institute demonstrate that TIMP-2 (tissue inhibitor of metalloproteinase 2) exerts a matrix metalloproteinase (MMP)-independent anti-angiogenic effect in vivo that is mediated by TIMP-2 binding to the alpha3 beta1 integrin receptor, facilitating protein tyrosine phosphatase activity. This anti-angiogenic effect is in addition to TIMP-2 regulation of the remodeling of the extracellular matrix through MMPs.

Development Status:
Identified a number of synthetic peptides that mimic linear sequences of TIMP-2 that bind the alpha3 beta1 integrin receptor, retaining anti-angiogenic activity in vitro and in vivo.

Further R&D Required:

• Development of additional TIMP-2 mimetic peptides with enhanced angiogenic activities.
• Synthesis of small molecule analogs of TIMP-2 mimetic peptides with angiogenic activity.
• Preclinical and clinical trials of synthetic TIMP-2 mimetic peptides and small molecule analogs.

IP Status:

• A patent application is being filed for TIMP-2 angio-inhibitory peptides.
• U.S. Patent No. 5,698,671 issued December 16, 1997
• U.S. Patent No. 5,595,885 issued January 21, 1997

Contact Information:
John D. Hewes, Ph.D., NCI Technology Transfer Center
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov

Reference:  #358 LZ

Updated 10/24/2007