A DNA repair inhibitor will help cancer treatment
Siberian scientists have discovered an enzyme that prevents the fight against cancer
Specialists of the Institute of Chemical Biology and Fundamental Medicine SB RAS and the Novosibirsk Institute of Organic Chemistry named after N.N. Vorozhtsov SB RAS found the reason for the insufficient effectiveness of anti-cancer drugs used in the clinic, such as topotecan and irinotecan.
Their action is hindered by the enzyme tyrosyl-DNA-phosphodiesterase 1 – it is he who removes the damage created by drugs in the DNA of carcinogenic cells. For the most effective therapy, it is necessary to inhibit it (that is, to suppress its activity), and now scientists are working on a drug with such an effect.
– In the process of chemotherapy or radiotherapy, the DNA structure in cancer cells is disrupted, – says Olga Ivanovna Lavrik, head of the Laboratory of Bioorganic Chemistry of enzymes of the IHBFM SB RAS, Corresponding member of the RAS, Professor Olga Ivanovna Lavrik. – However, all these damages are eliminated by DNA repair systems, the activity of which must be inhibited during treatment. The development of such tools is one of the main directions in modern medical chemistry.
In the course of fundamental research, scientists of the IHBFM SB RAS found the optimal target for suppressing the activity of repair systems – tyrosyl-DNA-phosphodiesterase 1. Further, the best inhibitors were selected from the library of natural compounds of the Department of Medical Chemistry of the NIOH SB RAS (head – Doctor of Chemical Sciences, Professor Nariman Faridovich Salakhutdinov). Specialists improved them with the help of organic synthesis, modeled the structures of these substances and selected two that have the greatest effect. Scientists successfully tested them on cells, and then on mice: the growth of the tumor grafted to rodents was suppressed by 60-70%, and metastasis in the lungs was completely destroyed. This result was obtained jointly with a group of the Federal Research Center Institute of Cytology and Genetics SB RAS. The work with the participation of experimental animals was headed by senior researcher at the Laboratory of Gene Expression Regulation, Candidate of Biological Sciences Nellie Alexandrovna Popova.
The structure of the compound, which inhibits the activity of the enzyme tyrosyl-DNA-phosphodiesterase 1, remains secret until the completion of the process of patenting the development, and, according to scientists, there are no analogues in the world yet. (In fact, the patent application RU 2581060 "A means for inhibiting the enzyme tyrosyl-dna-phosphodiesterase 1 person" is in the public domain, and those who wish can read all the secrets there, except, perhaps, the know-how – VM.)
According to Olga Ivanovna Lavrik, the price of the drug, if it enters the market, will be quite affordable – in the Department of Medical Chemistry of the Research Institute of the Siberian Branch of the Russian Academy of Sciences, they always try to make the synthesis of compounds – potential drugs as cheap as possible.
Now IHBFM SB RAS and NIOH SB RAS are working under a joint grant from the Russian Science Foundation, which is valid for two more years. In order to transfer the drug to preclinical trials, additional funding is needed, and scientists expect to receive it from the Ministry of Industry and Trade or the Ministry of Education and Science of the Russian Federation.
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19.07.2016