Pat.219802 Use of the composition of 3-bromopyruvate as a second application of a medicament for the treatment of fungal infections
Inventors: Mariusz Dyląg, Paweł Lis, Young H. Ko, Peter L. Pedersen, Andre Goffeau, Stanisław Ułaszewski
3-bromopyruvate (3BP) as an analog of a key cellular metabolite may be an alternative solution both in the treatment of cancer and cryptococcosis. The first research on this compound was initiated at Johns Hopkins University in Baltimore (MA, USA) by professor P.L. Pedersen and Dr. YH. Ko, who were the originators and pioneers of 3BP research. Further studies on the molecular level, conducted in close cooperation with a team led by professor S. Ułaszewski, including Dr. M. Dyląg and Dr. P. Lis from the University of Wrocław, have shown that this compound enters particularly easily into cancer cells, as well as into cells of pathogenic fungi of the genus Cryptococcus. This is mainly due to the presence of specific proteins transporting carboxylic acids and their derivatives through the cell membrane, thanks to which this compound reaches high and therapeutically effective intracellular concentrations. This compound, even in concentrations many times lower than those in which it causes a complete inhibition of cell growth and proliferation, leads to a drastic decrease in intracellular ATP concentration and, consequently, effectively disturbs the cell’s energy management.
3-BROMOPURYVATE IN CRYTOCOCCOSIS TREATMENT
According to the statistical data published by WHO, 19,292,789 cases of cancer were diagnosed only in 2020, of which less than 10 million were fatal. In turn, cryptococcosis, which has been in the area of our interest since 2013, is diagnosed annually in approximately 1 million patients, among whom 600,000 deaths are found each year. Many currently available drugs are ineffective in eradication of both disease entities, or are associated with significant toxicity. For this reason, finding new solutions both in the treatment of cancer and cryptococcosis is becoming an urgent problem.
As we have shown in our research, 3BP differentiated activity against cells of various fungal species, as well as mammalian healthy and cancer cells results in differences on the level of intracellular accumulation and uptake of this compound into the cell. The lack of cytotoxic and mutagenic activity of 3BP, demonstrated in studies on mammalian cell lines, became the basis for proposing pharmaceutical compositions of this compound effective in vitro in eradication of tumors (patent no.: US 10,500,175 B2) and cryptococcosis.
