The aim. To conduct a literature review of current data on the senolytic effects of dual BCL-xL/BCL-2 degraders, including available molecules, their mechanism of action, efficacy, and safety.

Materials and Methods. Literature search was performed in PubMed, Science Direct, and SciELO databases using the keywords: “senolytics”, “BCL-xL/BCL-2 dual degraders”, “proteolysis targeting chimeras”, “753b”, “WH244”. In the eLIBRARY.ru database were used the next keywords: «сенолитики», «двойные деградаторы BCL-xL/BCL-2», «протеолиз-направленные химеры», «753b», «WH244».

Results. The accumulation of a small number of senescent cells in the body, due to their release of the senescence-associated secretory phenotype (SASP), contributes to the elimination of old and damaged cells. However, when the number of senescent cells becomes large, SASP triggers a chronic inflammatory process that accelerates aging and leads to the development of age-related diseases such as cancer, diabetes mellitus, atherosclerosis, etc. Therefore, there is a need to develop senolytics — drugs aimed to eliminate senescent cells. One possible way to achieve this is through the pharmacological induction of apoptosis. According to literature data, a chimeric molecule, 753b, was created using PROTACs technology. One end of it binds to an E3 ligase, the other to anti-apoptotic proteins (BCL-xL or BCL-2). As a result, all these molecules are brought together in space, forming a ternary complex. Due to proximity, the E3 ligase attaches ubiquitin molecules to the anti-apoptotic proteins, after which the proteasome destroys them. When BCL-xL and BCL-2 are degraded, apoptosis of senescent cells occurs. The molecule 753b is classified as a first-generation dual BCL-xL/BCL-2 degrader. Its anti-senescence and anti-tumor efficacy has been demonstrated in preclinical studies without the development of significant thrombocytopenia. Based on molecule 753b, a more potent analog was developed through two modifications — molecule WH244, which is classified as a second-generation dual BCL-xL/BCL-2 degrader.

Conclusion. Considering the data on efficacy and safety presented in the literature sources, further comprehensive research on molecules 753b, WH244, and/or their derivatives is required, including in clinical studies.

Currently, there is an increasing interest in studying the chemical composition of the above-ground part of Phacelia tanacetifolia Benth., honey based on the plant, individual biologically active compounds, and results of studying the pharmacological activity of this promising species are emerging.

The aim. To conduct a review and systematization of scientific data on the chemical composition, and application in medicine and pharmacy of the promising plant Phacelia tanacetifolia.

Materials and Methods. For searching scientific literature, data posted in the electronic databases elibrary.ru, Cyberleninka, Google Scholar, and PubMed were used. Publication search was conducted for the period from January 2001 to January 2026. The final number of works included in this review was 69.

Results. As a result of analyzing scientific literature data, the work characterizes the Boraginaceae family, the Phacelia genus, and the Phacelia tanacetifolia species; the main groups of biologically active compounds and the chemical composition of the studied object. The main aspects of studying Phacelia tanacetifolia as a honey-producing plant and green manure are presented. The results of the pharmacological activity of phacelia honey are presented. The potential pharmacological activity of Phacelia tanacetifolia is formulated.

Conclusion. A comprehensive search for information on Phacelia tanacetifolia abroad and in Russia has been conducted. Based on the results of the work, the expediency of a deeper study of the selected plant object for its application in medicine and pharmacy is justified.

The aim. To determine the content of flavonoids in aqueous and aqueous-alcoholic extracts from the herbs of Astragalus varius and Astragalus testiculatus and to investigate the antidepressant effect of the extracts in vivo.

Materials and methods. The objects of the study were dried and ground herbs of Astragalus varius S.G. Gmel. and Astragalus testiculatus Pall., collected in the Saratov region during the period of mass flowering (May–June 2021). Aqueous (1:10) and aqueous-alcoholic (1:10, extractant 70% ethanol) extracts were obtained from the raw material. The flavonoid content was determined by differential spectrophotometry at an analytical wavelength of 410 nm in quartz cuvettes with l=1 on a Shimadzu UV-1800 spectrophotometer (Shimadzu, Japan). The study of antidepressant activity was conducted on male mice weighing 32–38 g and aged 2–3 months using the Tail Suspension Test (TST). The animals received the studied extracts at a dose of 100 mg/kg, and amitriptyline at a dose of 10 mg/kg served as the comparison drug. For data evaluation, the Mann-Whitney U-test and Bonferroni correction (p <0.01) were used. To study the strength of the linear relationship between antidepressant activity and flavonoid content, correlation analysis was used (Spearman correlation coefficient at p <0.05).

Results. The flavonoid content in aqueous and aqueous-alcoholic extracts from the herb of Astragalus varius was 2.54 ± 0.04% and 9.31 ± 0.07%, respectively, and in extracts from the herb of Astragalus testiculatus — 1.06 ± 0.05% and 10.34 ± 0.05%, respectively. The aqueous-alcoholic extract of Astragalus testiculatus demonstrated a pronounced effect reliably similar to amitriptyline (p = 0.01) both after a single oral administration and throughout the entire experimental period (21 days). The aqueous-alcoholic extract of Astragalus varius did not show an antidepressant effect after a single administration; however, on days 8, 15, and 21 of administration, a significant (p = 0.01) effect was observed in the animals. Upon administration of the aqueous extract of Astragalus varius, an antidepressant effect was observed on days 1, 15, and 21 of the study (p = 0.01); however, the effect was absent on day 8 of the experiment. The aqueous extract of Astragalus testiculatus, both after single and chronic oral administration of the extract to animals, showed no activity in the experiment (p >0.01).

Conclusion. Aqueous-alcoholic extracts from the herbs of both species exhibited a more pronounced antidepressant effect compared to aqueous extracts. Correlation analysis established that the identified antidepressant activity is associated with the flavonoid content in the studied extracts.

Molecular design and synthesis of a new series of biologically active azomethines containing a sterically hindered phenolic fragment were carried out. Within the scope of the study, 8 compounds were synthesized, and their antioxidant activity was evaluated under in vitro conditions. To establish the mechanism of action, molecular docking was used to model the interaction of the synthesized ligands with the active site of glutathione peroxidase-4 (GPx-4). The conducted analysis revealed key structural features determining antioxidant efficacy and established a correlation between molecular structure and biological activity.

The aim. Synthesis, computer screening, and investigation of the antioxidant properties of new azomethines based on sterically hindered phenol, as well as establishing structure–activity relationships.

Materials and methods. A new series of 2,6-di-tert-butyl-4-[C-alkyl-(aryl)-(N-phenyl)-azomethine]phenols was synthesized by the condensation of corresponding ketones with aromatic amines in the presence of catalytic amounts of p-toluenesulfonic acid. The structure and purity of the obtained compounds were confirmed by a complex of physicochemical methods, including IR spectroscopy, H NMR spectroscopy, and elemental analysis. For the initial assessment of the biological potency of the synthesized compounds, computer prediction (in silico) of their antioxidant, antiradical, and cardiotonic properties was performed using the online platform PASS Online. Molecular modeling of potential inhibitory activity against human glutathione peroxidase-4 (GPx-4) was carried out using the Autodock 4.0 program. The conformational mobility of the ligands was taken into account, for which optimal torsion angles were previously determined and set. Experimental study of antioxidant activity (AOA) was conducted in two model systems: induction of lipid peroxidation (LPO) in a complex of corn oil fatty acids under UV irradiation; and the Fenton system (H₂O₂/Fe²⁺). To compare efficacy, ubiquinone and bottled hydroxytoluene (BHT, the active substance of the drug dibulin), representing the class of sterically hindered phenols, were used as reference standards.

Results. The spectrum of biological activity of the studied compounds was predicted in silico using the PASS Online service. As it was expected, all substances have cardiotonic, membrane-stimulating, and antioxidant potential. The presence of AOA and the ability to scavenge free radicals allows these molecules to be classified as antiradical agents. Experimental verification of AOA was carried out in two model systems: based on photooxidation (UV irradiation) of a complex of fatty acids from corn oil (system No. 1) and on the Fenton system (H₂O₂/Fe²⁺, system No. 2). In all the cases, the studied compounds demonstrated high efficacy, inhibiting lipid peroxidation LPO by 42–48%. This result significantly exceeds the activity of standard antioxidants — ubiquinone (11%) and BHT (39%) — in the same conditions.

Conclusion. The results of molecular docking indicate a high affinity of the new ligands to the GP-4 protein, with the calculated binding energy for the most promising structures being comparable to that of known standards—ubiquinone, dibulin (hydroxybutylated toluene), and mexidol. In vitro experimental data confirmed the pronounced antioxidant activity of the synthesized compounds. “Lead” structures were identified that surpass classical antioxidants—ubiquinone and dibulin — in efficacy.

Antiangiogenic therapy, despite its effectiveness, is limited by systemic toxicity, the development of organism resistance, and high treatment costs. In this regard, the development of new, safer, and more effective antiangiogenic agents is a relevant task in modern oncology.

The aim. Assessment of toxicological characteristics and experimental substantiation of the optimal range of therapeutic doses of an NOS/PDK inhibitor (compound T1084) for enteral administration.

Materials and methods. The study was conducted on 118 BALB/c mice and 79 F1 hybrids (CBA×C57BL/6j). The acute toxicity of compound T1084 was studied following a single enteral administration. Cumulative effects were assessed using the Lim method with parenteral administration. The optimal range of anti-tumor doses was investigated on a model of Ehrlich’s solid carcinoma therapy with subchronic enteral administration of compound T1084 at doses of 200–400 mg/kg.

Results. Parameters of acute toxicity for compound T1084 upon enteral (intragastric) administration were established: LD₁₀ — 2031 mg/kg, LD₁₆ — 2100 mg/kg, LD₅₀ — 2356±15 mg/kg, LD₈₄ — 2644 mg/kg. According to toxicological studies, compound T1084, when administered enterally, belongs to hazard class III (moderately hazardous substances) according to GOST 12.1.007–76 and class V according to GOST 32419–2022 for the EAEU. A 5-fold decrease in the toxicity of T1084 was revealed with enteral administration compared to parenteral administration. The absence of cumulative properties in T1084 was established, which allows for prolonged courses of this compound. On the Ehrlich’s carcinoma therapy model, a dose-dependent anti-tumor effect was shown: at 200 mg/kg, tumor growth inhibition (TGI) was 15–20%; 300 mg/kg — 28–31%; 400 mg/kg — 30–35%. The absence of significant differences between doses (300 and 400 mg/kg) with more favorable tolerability allowed the selection of 300 mg/kg as the optimal dose.

Conclusion. The obtained data substantiate the promise of preclinical development of an oral dosage form of T1084 for long-term therapy in oncology, including in adjuvant treatment regimens.

Infantile hemangioma (IH) is a benign vascular neoplasm, occurring in 4–10 % of newborns and requiring timely therapy in cases of complicated progression. Currently, propranolol is recognized as the "gold standard" for IH treatment due to its proven efficacy and safety. However, in the Russian Federation, there are no readily available dosage forms (DFs) of propranolol for children, which creates a significant problem for pediatric practice. In this regard, the development of a PF that ensures accurate dosing and ease of use in children is relevant.

The aim. To develop the composition and technology for obtaining orodispersible mini-tablets (OMT) of propranolol hydrochloride for children using the Quality by Design (QbD) approach.

Materials and methods. The active pharmaceutical substance of propranolol hydrochloride and excipients were used: mannitol, microcrystalline cellulose 102 (MCC 102), crospovidone (CPV), sodium saccharin dihydrate, sodium stearyl fumarate (SSF), and colloidal silicon dioxide. The composition development was carried out using the QbD methodology, with experimental design planned using the Mixture Design (MD) method. The independent variables were the content of MCC 102, CPV, and SSF. OMT with a diameter of 3 mm were obtained by direct compression. The tablet blend and OMT were tested according to the methods presented in the State Pharmacopoeia of the Russian Federation, XV edition: flowability, bulk density and tapped density, crushing strength, friability, disintegration, and mass uniformity. The dose uniformity of the optimized composition was determined by HPLC.

Results. During the first stage, the target quality profile of the OMT was determined. In accordance with this, critical quality attributes (CQAs) were established: for the powder blend  – flowability, bulk density, tapped density; for the OMT – crushing strength, disintegration, friability, and dose uniformity. A composition was developed and optimized, which allowed the required values for all CQAs to be achieved. Statistical analysis revealed significant inter-component interactions affecting the crushing strength and disintegration of the OMT.

Conclusion. The composition and technology for obtaining orodispersible mini-tablets of propranolol hydrochloride have been developed.

Related to the article: Lukina E.A., Ponomarev R.V., Trishina S.V., Gabitova E.S., Vashakmadze N.D., Karkashadze G.A., Namazova-Baranova L.S. Interim results of the first stage of a multicenter open multi-cohort study of the safety, pharmacokinetics, pharmacodynamics and efficacy of veranafusp alfa in adult patients with mucopolysaccharidosis type II. Pharmacy & Pharmacology. 2026;14(1):81-96. https://doi.org/10.19163/2307-9266-2026-14-1-81-96

We hereby inform readers that changes have been made to the final version of the article in Russian.

In the published article “Interim results of the first stage of a multicenter open multi-cohort study of the safety, pharmacokinetics, pharmacodynamics and efficacy of veranafusp alfa in adult patients with mucopolysaccharidosis type II”, the authors discovered a technical error: figures 4 and 5 were randomly rearranged in the article relative to the captions to the figures.

Рисунок 4 — Динамика изменения уровня дерматансульфата в спинномозговой жидкости (медиана) взрослых пациентов
с мукополисахаридозом II типа,
получавших 3 мг/кг веренафусп альфа.

Рисунок 5 — Динамика изменения уровня гепарансульфата в спинномозговой жидкости (медиана) взрослых пациентов
с мукополисахаридозом II типа,
получавших 3 мг/кг веренафусп альфа.

Сorrect version:

Рисунок 4 — Динамика изменения уровня дерматансульфата в спинномозговой жидкости (медиана) взрослых пациентов
с мукополисахаридозом II типа,
получавших 3 мг/кг веренафусп альфа.

Рисунок 5 — Динамика изменения уровня гепарансульфата в спинномозговой жидкости (медиана) взрослых пациентов
с мукополисахаридозом II типа,
получавших 3 мг/кг веренафусп альфа.

The authors regret that, probably due to an oversight in the originally published version of this article, Figures 4 and 5 were rearranged relative to the captions to the figures. The error is technical in nature, it does not change the essence of the data presented in the article, but it may affect their correct perception by readers. The English version of the article is correct.

The original article in Russian has been updated in the online version: https://www.pharmpharm.ru/jour/article/view/1814