Cysteine-Modifying Substrate Analogue Inhibitors of Ribose 5-Phosphate Isomerase

Description:

Reference #: 01181

The University of South Carolina is offering licensing opportunities for strong selective inhibitors of the ribose 5-phosphate isomerase enzyme as new drug alternatives to commonly prescribed therapies for Chagas’ disease, African sleeping sickness, and leishmaniasis.

Invention Description:

Kinetoplastid parasites such as Trypanosoma cruzi (T. cruzi), Trypanosoma brucei (T. brucei), and the Leishmania species utilize and depend on the pentose phosphate pathway (PPP) for survival. Obstruction of this pathway leads to cell death. This can be achieved by using drugs to inhibit ribose 5-phosphate isomerase (RPI), a type B enzyme found in protozoan parasites. 

The subject invention describes experimentally-confirmed, selective inhibitors of protozoan RPI. These compounds only target type B enzymes, bypassing human RPI, which are considered type A.

Potential Applications:

The compounds offer an alternative to current drugs used to treat three diseases of the trypanosome: American trypanosomiasis (Chagas' disease), which is caused by the T. cruzi parasite; human African trypanosomiasis (African sleeping sickness), which is caused by the T. brucei parasite; and leishmaniasis, which is caused by the Leishmania species of parasites. They may also be adapted to treat malaria, schistosomaisis (snail fever), and filarial diseases.

Advantages and Benefits:

These inhibitors selectively bind and block protozoan RPI and avoid cross-reactivity with the human homologue, giving rise to a good selectively ratio.

Background:

Current treatments for kinetoplasid diseases require substantial improvements in their tolerability, safety, and efficacy. New drugs that bind strongly to drug targets found in these parasites are needed to effectively combat resistance to current drugs. RPI enzyme inhibitors provide a viable alternative to existing therapies.

Development:

These inhibitors are currently being synthesized, after which they will be tested for enzymatic inhibition. Future development will proceed to drug testing in vitro parasite survival studies and in vivo infectivity studies.

 

 

 

Patent Information:
For Information, Contact:
Technology Commercialization
University of South Carolina
technology@sc.edu
Inventors:
Edward D'antonio
Keywords:
© 2018. All Rights Reserved. Powered by Inteum