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Therapeutics Based On The Induced Internalization Of Surface Receptors

The National Cancer Institute, Laboratory of Cellular Oncology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize therapeutics for diseases or conditions associated with target receptors, such as cancer, angiogenesis, or HIV infections.

Cell-surface receptors are responsible for the biological activities of many molecules.  Specific ligands bind to them, causing the cell-surface receptors to internalize or bring the receptor and ligand inside the cell.  A number of diseases, including cancer, metabolic disorders, and viral infections are known to require the expression of cell-surface receptors for critical pathogenetic steps. This has prompted significant research efforts toward the development of pharmaceutical agents that block the signals from cell-surface receptors. While this current research shows great promise, there is a strong need for new therapeutic strategies that utilize the mechanistic properties of cell-surface receptors.

This technology describes a strategy for artificially inducing the internalization of surface receptors, and thereby blocking the effects of the ligands associated with that receptor. This method employs bifunctional ligands that bind to both a scavenger receptor and a target receptor. As proof of concept, the inventors have shown that a ligand capable of binding to the scavenger receptor SREC-1 and the neuropilin-1 receptor NRP1 induces the internalization of NRP1 and inhibits NRP1 signaling. This strategy can be used to inhibit signaling from any target receptor if an appropriate bifunctional ligand is used. This approach could be used to limit tumor angiogenesis, limit tumor growth, block metastasis formation, block inflammation, block viral infection, and treat diseases where a cell surface receptor is identified as the molecular basis for disease.

Further R&D Needed:  Development of therapeutic analogues and test for efficacy and toxicity.

R&D Status:  Pre-clinical development.

IP Status:  U.S. Provisional Application No. 61/023,397 filed 24 Jan 2008

Value Proposition:

  • Method of inducing the internalization of target receptors
  • Ability to inhibit numerous diseases associated with target receptors such as HIV infection and cancer
Contact Information:
John D. Hewes, Ph.D.
NCI Technology Transfer Center
Tel: 301-435-3121
Email: hewesj@mail.nih.gov
Please reference advertisement # 763
Revised 12/29/2008


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Page Last Updated: 12-17-2008