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Peptide and Peptidomimetic Inhibitors of Smoothened Protein as Anti-neoplastic Agents

Posted Jun 09 2010 5:00pm

Description of Invention:
Cancer is caused by the improper regulation of certain signaling proteins in the cell. One of these pathways is the Hedgehog/Patched (HH/PTCH) pathway. Hedgehog is a secreted protein involved in the growth and development of embryonic cells. Patched is the receptor for hedgehog proteins and regulates a membrane protein called Smoothened (SMO). This pathway is activated in many tumor cells, including those in prostate, pancreas, stomach, and small cell cancer.

The technology is directed towards several synthetic peptides (including all-D analogs) corresponding to specific region of the SMO protein. Experiments in vitro demonstrate that they potentially suppress the growth of cancer cells and inhibit the expression of the HH/PTCH pathway genes. These novel SMO inhibitors are much more effective in inhibiting cell growth than currently available cyclopamine and cyclopamine derivatives. These novel peptides and their metabolically more stable analogs have a high potential for cancer therapy. Due to their high hydrophobic properties, these can be easily formulated for specific intratumor delivery or topical creams for skin disorders.

Applications:
  • A potent, highly soluble cancer therapeutic
  • Novel compounds that inhibit HH/PTCH pathway genes
  • Skin permeable compounds that can be formulated into tropical creams for skin malignancies treatment and prevention and treatment of psoriasis


Development Status:
The technology is currently in the pre-clinical stage of development.

Inventors:
Nadya I Tarasova (NCI)
Michael C Dean (NCI)
Hong Lou (NCI)


Patent Status:
HHS, Reference No. E-014-2007/0
US, Application No. 12/513,091 filed 30 Apr 2009


Relevant Publication:
  1. L Covic et al. Activation and inhibition of G protein-coupled receptors by cell-penetrating membrane-tethered peptides. Proc Natl Acad Sci USA. 2002 Jan 22;99(2):643-648. [ PubMed abs ]


Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The NCI-Frederick Structural Biophysics Laboratory is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Peptide and Peptidomimetic Inhibitors of Smoothened Protein as Anti-neoplastic Agents. Please contact John Hewes, Ph.D., at 240-482-3453 for more information.


Portfolios:
Cancer
Cancer - Therapeutics
Cancer - Research Materials
Internal Medicine
Internal Medicine - Therapeutics
In-vitro Data



For Additional Information Please Contact:
Jennifer Wong
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: wongje@mail.nih.gov
Phone: 301-435-4633
Fax: 301-402-0220


Ref No: 1479

Updated: 06/2010

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