Promising New Compounds in the Treatment of Prostate Cancer

Prostate specific membrane antigens offers new targets for potential prostate cancer drugs.

Eleven new promising compounds have been identified for the treatment of prostate cancer.

Prostate specific antigens (PSA) are a well-known marker already used for the diagnosis of prostate cancer, but is still considered an insufficiently precise target. However, another promising alternative for prostate cancer diagnosis and treatment is prostate specific membrane antigen (PSMA).

“PSMA is one of the most promising biological targets for the development of new hybrids of selective PSMA ligands with antitumor medicinal substances or molecular diagnostic tools for their targeted delivery to the site of the disease — particularly in the case of prostate cancer,” said Yan Andreevich Ivanenkov, PhD, Head of the Laboratory of Medical Chemistry and Bioinformatics.

PSMA catalyzes the hydrolysis of N-acetylaspartylglutamate into N-acetylaspartate and glutamate, and was used to help create a list of the most promising substances in prostate cancer treatment.

An article published in the Journal of Drug Targeting noted all molecules that are able to bind to PSMA can be divided into 3 categories: antibodies, aptamers, and ligands.

When the 3 groups were compared, researchers found that ligands were the most promising group, because of the size and weight that are best suited for synthesizing. Additionally, ligands also have solid pharmacokinetic parameters.

Since the 1990s, scientists have been looking for a ligand compatible with PSMA. One of the first discovered were phosphorus compounds that showed high efficacy on cancer cells. However, phosphorus compounds had insufficient pharmacokinetic parameters for clinical trials.

Additionally, compounds with —SH groups have become alternatives to phosphorus-containing chemicals. These had high bioavailability when the medication was taken orally and were also able to better penetrate the cell membrane. However, the drugs had insufficient selectivity and metabolic stability.

Currently, compounds formed on the basis of urea are the most widely studied PSMA ligands type. Urea or carbamide is used for the excretion of nitrogen-containing waste from the organism by mammals.

Urea modifications, nitrosourea, and similar compounds have been used for chemotherapy for a long time.

“It is impossible to give a precise answer to the question of how soon PSMA ligands will appear in the clinic,” said researcher Anastasia Aladinskaya. “On average, the development of a new medication can take up to 10 years. Currently, these molecules (as potential drugs for the diagnosis of prostate cancer) are in the first and second phases of clinical trials. However, the fact that the PSMA-diagnostics allows the monitoring of tumor growth and development of metastasis, makes this an attractive target for future developments of drugs. The first results are already there, and they are very promising.”