Tumor Targeting by Small Molecule Therapeutics for a Proton-Coupled Folate Transporter (PCFT)

Case ID:

WSU researchers, in collaboration with Duquesne University, have isolated a unique series of pyrrolopyrimidine antifolate analogs that show selective cytotoxicity toward solid tumors such as ovarian, prostate, or breast cancer cells.

Background & Unmet Need:

Protein-coupled folate transporters (PCFT) play an important role in intestinal folate absorption.  PCFTs are part of a family of various proton-coupled low pH transport systems that mediate intestinal folate absorption of essential nutrients including vitamins, amino acids, peptides, metal-ions and various organic anions.  Moreover, PCFT exhibits an extremely high transport affinity for the antifolate anticancer drug pemetrexed (Alimta).  Targeting these receptors has great clinical potential in the treatment of tumors.


Technology Description:

This invention is a newly synthesize group of cytotoxic folate analogs that are selective for PCFT.  The analogs are similar to the clinically used antifolate drug Alimta.  Many solid tumors differ from normal tissue due to their acidic environment.  PCFTs have an acidic pH optimum of 5.5-6.5 required for transport so selective targeting of solid tumors expressing PCFT with small molecule inhibitors allows for the selective destruction of tumor cells.  Alimta also selects for receptor folate carriers, thereby compromising potential tumor selectivity.  Our analogs show specific selectivity for PCFT and thus provide a more targeted therapy. 


Commercial Applications:

  • Antitumor drugs that target tumors expressing PCFT
  • Treatments for ovarian, prostate, and breast cancers


Stage of Development:



Competitive Advantages:

  • A less toxic cancer treatment that targets solid tumor cells
  • Provides a more targeted therapy than current drugs
  • The only known cytotoxic folate analog that is selective for PCFT


Intellectual Property Status:

US patent and PCT applications filed


Related Publications or Citations of Work:

Gangjee A, Zeng Y, McGuire JJ, Mehraein F, Kisliuk RL. (2004) Synthesis of classical, three-carbon-bridged 5-substituted furo[2,3-d]pyrimidine and 6-substituted pyrrolo[2,3-d]pyrimidine analogues as antifolates.  J Med Chem. 47(27):6893-901.


Patent Information:
For Information, Contact:
Joan Dunbar
Associate Vice President for Technology Commercialization
Wayne State University
(313) 577-5542
Larry Matherly
Aleem Gangjee
Analog or Analogue
Breast Cancer
Cancer Therapies
Drug Delivery
Ovarian Cancer
Prostate Cancer