MISiS and Izvarino Pharma: Docetaxel-based drug for the treatment of prostate cancer

Main articles:

• Cancer (cancer)
• Prostate cancer (prostate)

2021: Development of a drug for the treatment of prostate cancer

Russian scientists have developed a drug for the treatment of prostate cancer based on a substance obtained from the needles of a European yew. This was announced on November 20, 2021 by MISiS. During the tests, the drug showed effectiveness above 80%. At the same time, it acts aimed at specific tumor cells, due to which the total toxic effect on the body is reduced by 20%. The work is published in the journal European Journal ofMedicinal Chemistry.

Prostate carcinoma is the second most common cancer among men and the fifth most common cause of death among cancer patients. According to the portal Global Cancer Observatory, only in 2020 prostate cancer caused 375 thousand deaths. In total, 1.4 million cases were recorded in the world in 2020.

At the same time, many drugs used to treat cancer 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 into tumor cells, avoiding unwanted side effects. But in order to ensure the selectivity of the drug, some specific marker is needed that will allow you to identify and target tumor cells.

Prostate carcinoma cells contain a prostatic specific membrane antigen (PSMA) in substantially 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 the substance a suitable marker for targeted delivery of therapeutic drugs.

A group of Russian scientists from Moscow State University named after M.V. Lomonosov, MIPT and NITU "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 feature is increased, compared to analogues, bioavailability due to low molecular weight. Docetaxel - a substance to science has long been known, it is used for the therapy 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 tumor cells associated with docetaxel using a peptide ligament. Due to this formula, increased antitumor efficacy is achieved and toxic effect of docetaxel on the body is reduced.

In this work, we obtained low molecular weight conjugates of docetaxel with PSMA ligands. Previously, conjugates for the treatment of prostate cancer based on this docetaxel have been known, but all previous developments have been high molecular weight delivery systems or nanoparticle-based carriers. The main advantages of the low molecular weight conjugates obtained by us are mainly related to their pharmacokinetics, since they, unlike larger delivery objects, usually have a short circulation time. Any small conjugate that is not captured by the target cell will be quickly removed from the body, thereby reducing the possibility of releasing a drug outside the target and the associated toxicity of the drug, "explained Alexei Machulkin, Ph.D., researcher at the Department of Organic Chemistry of Moscow State University named after M.V. Lomonosov.

At the same time, the resulting drug turned out to be almost 20% less toxic than docetaxel in pure form. The prepared preparation has high antitumor efficiency with high solubility and reduced side effects.

Tests showed that the drug we developed restrains tumor growth with an efficiency of more than 80% at a dosage of 30 mg/kg. The effectiveness at the cellular level was demonstrated with the help of special sensors developed in the biophysics laboratory of NITU "MISiS," "added Alexander Erofeev, Ph.D., Head of the NIL of Biophysics of NITU" MISiS. "