Inducing Cancer Cell Death by Inhibition of GPCR Signaling Based on the Tumor Microenvironment


Damien Thevenin, at Lehigh University has developed a compound, pH (low) insertion peptide (pHLIP), which can selectively target tumors based on their low extracellular pH, while sparing healthy tissues and preventing off-target toxicity. This delivery peptide can be conjugated to soluble peptides capable of inhibiting the activity of G-protein coupled receptors (GPCRs) at the intracellular surface.


• Provides a second mechanism for tumor targeting based on low extracellular pH, overcoming the limitations associated with traditional GPCR targeting approaches (antibodies,small molecules) and preventing off-target effects

• Conjugates are selectively delivered to tumor cells with delivery across the cell membrane, sparing healthy cells and preventing systemic toxicity.

• pHLIP can be conjugated to an infinite number of peptides targeted to molecular targets promoting a malignant phenotype.

• Causes potent tumor growth inhibition with decreased GPCR activity without plasmamembrane disruption, cost-effective, non-immunogenic

Lehigh University Tech ID # 070715-01


GPCRs, the largest family of cell surface receptors, have been implicated in neoplastic transformation of many cancers. Associated with controlling many aspects of cellular function, GPCRs have recently emerged as crucial players in tumor growth, survival, invasion and metastasis. Although GPCR-targeted drugs constitute approximately 40% of all marketed therapeutics, there is a lack of development for cancer therapies. Existing targeting methods rely on GPCR overexpression in cancer cells, and many may be limited due to difficulties with receptor selectivity, resulting in off-target toxicity and therapeutic resistance. There is a significant need for technologies, which facilitate drug delivery and binding of highly specific, active molecules to inhibit GPCR activity in tumors.

Lehigh University is looking for a partner for further development and commercialization of this technology through a license. The inventor is available to collaborate with interested companies.

App Type Country Serial No. Patent No. File Date Issued Date Expire Date
Provisional [PR] United States 62/192,828 7/15/2015    
For Information, Contact:
Thomas Meischeid
Interim Director
Lehigh University
Damien Thevenin