Tuned docetaxel
European yew tree against prostate cancer
MSU Press Center
Russian scientists have developed a new drug for the treatment of prostate cancer based on a substance derived from European yew needles. During the tests, the drug showed an effectiveness above 80%. At the same time, it acts specifically on specific tumor cells, thereby reducing the overall toxic effect on the body by 20%. The work was published in the European Journal of Medicinal Chemistry (Machulkin et al., PSMA-targeted small-molecule docetaxel conjugate: Synthesis and preclinical evaluation).
Prostate carcinoma is the second most common cancer among men and the fifth most common cause of death among cancer patients. According to the Global Cancer Observatory portal, prostate cancer caused 375 thousand deaths in 2020 alone. In total, 1.4 million cases were registered in the world last year.
At the same time, many drugs used for the treatment of oncological diseases have a detrimental effect not only on cancer, but also on healthy cells of the body. A possible solution to the problem may be targeted delivery of drugs directly to the tumor cells, avoiding undesirable side effects. But in order to ensure the selectivity of the drug, some specific marker is needed that will allow identifying and targeting tumor cells.
Prostate carcinoma cells contain prostate specific membrane antigen (PSMA) in significantly larger volumes than healthy prostate cells, and the more aggressive the tumor, the higher the concentration of this antigen in it. Accordingly, the increased concentration of PSMA in prostate carcinoma cells makes this substance a suitable marker for targeted delivery of therapeutic drugs.
A group of Russian scientists from Lomonosov Moscow State University, MIPT and NUST MISIS, together with the pharmaceutical company Izvarino Pharma, developed a combined drug based on docetaxel, an active substance of plant origin obtained by chemical synthesis from needles of European yew (Taxus baccata). Its peculiarity is its increased bioavailability compared to analogues due to its low molecular weight. Docetaxel is a substance known to science for a long time, it is widely used for the treatment of metastasized prostate carcinoma resistant to hormone therapy. The drug developed by Russian scientists consists of a vector molecule that is responsible for delivering the active substance to the tumor cells associated with docetaxel using a peptide bundle. Due to this formula, increased antitumor efficacy is achieved and the toxic effect of docetaxel on the body is reduced.
"In this work, for the first time, we obtained low-molecular conjugates of docetaxel with PSMA ligands. Previously, conjugates for the treatment of prostate cancer based on this docetaxel were already known, but all previous developments were high-molecular delivery systems or carriers based on nanoparticles. The main advantages of the low molecular weight conjugates obtained by us are mainly related to their pharmacokinetics, since they, unlike larger delivery facilities, usually have a short circulation time. Any small conjugate that is not captured by the target cell will be quickly eliminated from the body, thereby reducing the possibility of drug release outside the target and the associated toxicity of the drug," explains Alexey Machulkin, Ph.D., researcher at the Department of Organic Chemistry of Lomonosov Moscow State University.
At the same time, the resulting drug turned out to be almost 20% less toxic than docetaxel in its pure form. The resulting drug is characterized by high antitumor efficacy with high solubility and reduced side effects.
"Tests have shown that the drug we developed restrains tumor growth with an efficiency above 80% at a dosage of 30 mg/kg. The effectiveness at the cellular level was demonstrated using special sensors developed in the Laboratory of Biophysics of NUST MISIS," adds Alexander Erofeev, Ph.D., Head of the NUST Biophysics Research Institute "Misis."
Portal "Eternal youth" http://vechnayamolodost.ru