title: ÐÐ·ÑÑÐµÐ½Ð¸Ðµ ÑÐµÑÐ°Ð¿ÐµÐ²ÑÐ¸ÑÐµÑÐºÐ¾Ð³Ð¾ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»Ð° Ð½Ð¾Ð²ÑÑ Ð½Ð¸Ð·ÐºÐ¾Ð¼Ð¾Ð»ÐµÐºÑÐ»ÑÑÐ½ÑÑ Ð¿ÑÐ¾ÑÐ¸Ð²Ð¾Ð¾Ð¿ÑÑ Ð¾Ð»ÐµÐ²ÑÑ Ð¿ÑÐµÐ¿Ð°ÑÐ°ÑÐ¾Ð² Ð½Ð° Ð¿ÑÐ¸Ð¼ÐµÑÐµ Ð¼ÐµÑÐ°ÑÑÐ°ÑÐ¸ÑÐµÑÐºÐ¾Ð¹ Ð¼ÐµÐ»Ð°Ð½Ð¾Ð¼Ñ Ð»ÐµÐ³ÐºÐ¸Ñ
title: Ð²ÑÐ¿ÑÑÐºÐ½Ð°Ñ ÐºÐ²Ð°Ð»Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¾Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¼Ð°Ð³Ð¸ÑÑÑÐ°
titleType: Subtitle
title: Study of the therapeutic potential of new low-molecular-weight anticancer drugs on the example of metastatic lung melanoma
Creators: name: Ð Ð¾Ð³Ð¾Ð²Ð°, ÐÐ½Ð½Ð°
Publisher: name: Ð¡Ð°Ð½ÐºÑ-ÐÐµÑÐµÑÐ±ÑÑÐ³ÑÐºÐ¸Ð¹ Ð¿Ð¾Ð»Ð¸ÑÐµÑÐ½Ð¸ÑÐµÑÐºÐ¸Ð¹ ÑÐ½Ð¸Ð²ÐµÑÑÐ¸ÑÐµÑ ÐÐµÑÑÐ° ÐÐµÐ»Ð¸ÐºÐ¾Ð³Ð¾
Year: 2023
Subjects: Ð¼ÐµÑÐ°ÑÑÐ°ÑÐ¸ÑÐµÑÐºÐ°Ñ Ð¼ÐµÐ»Ð°Ð½Ð¾Ð¼Ð°
PARP
BRAF
Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾ÑÑ
Ð¼Ð¾Ð»ÐµÐºÑÐ»ÑÑÐ½ÑÐ¹ Ð´Ð¾ÐºÐ¸Ð½Ð³
ÑÐºÑÐ¸Ð½Ð¸Ð½Ð³ in vitro
ÑÐµÑÐ°Ð¿Ð¸Ñ in vivo
metastatic melanoma
inhibitors
in vitro screening
in vivo therapy

description: ÐÐ°Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¿Ð¾ÑÐ²ÑÑÐµÐ½Ð° Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ñ ÑÐµÑÐ°Ð¿ÐµÐ²ÑÐ¸ÑÐµÑÐºÐ¸Ñ ÑÐ²Ð¾Ð¹ÑÑÐ² Ð½Ð¾Ð²ÑÑ Ð½Ð¸Ð·ÐºÐ¾Ð¼Ð¾Ð»ÐµÐºÑÐ»ÑÑÐ½ÑÑ ÑÐ¾ÐµÐ´Ð¸Ð½ÐµÐ½Ð¸Ð¹, ÐºÐ¾ÑÐ¾ÑÑÐµ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»ÑÐ½Ð¾ ÑÐ²Ð»ÑÑÑÑÑ Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾ÑÐ°Ð¼Ð¸ Ð¾ÑÐ½Ð¾Ð²Ð½ÑÑ Ð¼Ð¸ÑÐµÐ½ÐµÐ¹ Ð¿ÑÐ¸ Ð»ÐµÑÐµÐ½Ð¸Ð¸ Ð¼ÐµÐ»Ð°Ð½Ð¾Ð¼Ñ. ÐÐµÑÐ¼Ð¾ÑÑÑ Ð½Ð° ÑÐ¾, ÑÑÐ¾ Ð¼Ð½Ð¾Ð³Ð¸Ðµ ÑÐ¶Ðµ Ð¸Ð·ÑÑÐµÐ½Ð½ÑÐµ Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾ÑÑ Ð¼Ð¾Ð³Ð»Ð¸ Ð±Ñ Ð·Ð½Ð°ÑÐ¸ÑÐµÐ»ÑÐ½Ð¾ Ð¿Ð¾Ð²ÑÑÐ¸ÑÑ ÑÐµÑÐ°Ð¿ÐµÐ²ÑÐ¸ÑÐµÑÐºÑÑ ÑÑÑÐµÐºÑÐ¸Ð²Ð½Ð¾ÑÑÑ Ð¿ÑÐ¾ÑÐ¸Ð² Ð·Ð»Ð¾ÐºÐ°ÑÐµÑÑÐ²ÐµÐ½Ð½ÑÑ Ð½Ð¾Ð²Ð¾Ð¾Ð±ÑÐ°Ð·Ð¾Ð²Ð°Ð½Ð¸Ð¹, ÑÐ¾Ð»ÑÐºÐ¾ Ð½ÐµÐºÐ¾ÑÐ¾ÑÑÐµ Ð¸Ð· Ð½Ð¸Ñ Ð±ÑÐ»Ð¸ Ð²Ð½ÐµÐ´ÑÐµÐ½Ñ Ð² ÐºÐ»Ð¸Ð½Ð¸ÑÐµÑÐºÑÑ Ð¿ÑÐ°ÐºÑÐ¸ÐºÑ. Ð¡Ð»ÐµÐ´Ð¾Ð²Ð°ÑÐµÐ»ÑÐ½Ð¾, ÑÐ°Ð·ÑÐ°Ð±Ð¾ÑÐºÐ° Ð²ÑÑÐ¾ÐºÐ¾ÑÑÑÐµÐºÑÐ¸Ð²Ð½ÑÑ ÑÐ¿ÐµÑÐ¸ÑÐ¸ÑÐµÑÐºÐ¸Ñ Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾ÑÐ¾Ð², ÐºÐ¾ÑÐ¾ÑÑÐµ Ð±ÑÐ»Ð¸ Ð±Ñ Ð±ÐµÐ·Ð¾Ð¿Ð°ÑÐ½ÑÐ¼Ð¸ Ð¸ Ð¾Ð±Ð»Ð°Ð´Ð°Ð»Ð¸ ÐºÐ°ÑÐµÑÑÐ²Ð°Ð¼Ð¸, ÑÐ²Ð¾Ð¹ÑÑÐ²ÐµÐ½Ð½ÑÐ¼Ð¸ Ð»ÐµÐºÐ°ÑÑÑÐ²ÐµÐ½Ð½ÑÐ¼ ÑÑÐµÐ´ÑÑÐ²Ð°Ð¼, Ð¾ÑÑÐ°ÐµÑÑÑ Ð²ÐµÑÑÐ¼Ð° Ð°ÐºÑÑÐ°Ð»ÑÐ½Ð¾Ð¹. Ð Ð´Ð°Ð½Ð½Ð¾Ð¹ ÑÐ°Ð±Ð¾ÑÐµ Ð¸Ð·ÑÑÐ°Ð»Ð¸ÑÑ Ð½Ð¸Ð·ÐºÐ¾Ð¼Ð¾Ð»ÐµÐºÑÐ»ÑÑÐ½ÑÐµ Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾ÑÑ Ñ Ð³ÐµÑÐµÑÐ¾ÑÐ¸ÐºÐ»Ð¸ÑÐµÑÐºÐ¾Ð¹ ÑÑÑÑÐºÑÑÑÐ¾Ð¹ Ð¸Ð·-Ð·Ð° Ð¸Ñ Ð¿ÑÐµÐ¸Ð¼ÑÑÐµÑÑÐ², Ð²ÐºÐ»ÑÑÐ°Ñ Ð²Ð¾Ð·Ð¼Ð¾Ð¶Ð½Ð¾ÑÑÑ ÐºÑÑÐ¿Ð½Ð¾Ð¼Ð°ÑÑÑÐ°Ð±Ð½Ð¾Ð³Ð¾ Ð¿ÑÐ¾Ð¸Ð·Ð²Ð¾Ð´ÑÑÐ²Ð°, Ð¿ÑÐ¾ÑÑÑÑ Ð¼Ð¾Ð´Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ñ Ð¸ Ð¾ÑÐ¸ÑÑÐºÑ, Ð° ÑÐ°ÐºÐ¶Ðµ Ð²ÑÑÐ¾ÐºÐ¸Ð¹ Ð²ÑÑÐ¾Ð´ Ð¿ÑÐ¾Ð´ÑÐºÑÐ°. ÐÑÐ» Ð¿ÑÐ¾Ð²ÐµÐ´ÐµÐ½ ÑÐºÑÐ¸Ð½Ð¸Ð½Ð³Ð¾Ð²ÑÐ¹ Ð°Ð½Ð°Ð»Ð¸Ð· in vitro Ñ Ð¸ÑÐ¿Ð¾Ð»ÑÐ·Ð¾Ð²Ð°Ð½Ð¸ÐµÐ¼ ÐºÐ»ÐµÑÐ¾Ðº Ð¼ÐµÐ»Ð°Ð½Ð¾Ð¼Ñ B16-F10, ÑÑÐ¾Ð±Ñ Ð²ÑÑÐ²Ð¸ÑÑ Ð½Ð°Ð¸Ð±Ð¾Ð»ÐµÐµ ÑÑÑÐµÐºÑÐ¸Ð²Ð½ÑÑ ÐºÐ°Ð½Ð´Ð¸Ð´Ð°ÑÐ¾Ð² Ð´Ð»Ñ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ð¹ in vivo. ÐÐ½Ð°Ð»Ð¸Ð· Ð¿ÑÐ¸ Ð¿Ð¾Ð¼Ð¾ÑÐ¸ Ð¼Ð¾Ð»ÐµÐºÑÐ»ÑÑÐ½Ð¾Ð³Ð¾ Ð´Ð¾ÐºÐ¸Ð½Ð³Ð° Ð²ÑÑÐ²Ð¸Ð» Ð¿ÑÐµÐ´ÑÐºÐ°Ð·Ð°Ð½Ð½ÑÐ¹ Ð¼ÐµÑÐ°Ð½Ð¸Ð·Ð¼ Ð´ÐµÐ¹ÑÑÐ²Ð¸Ñ ÑÐµÑÑÐ¸ÑÑÐµÐ¼ÑÑ ÑÐ¾ÐµÐ´Ð¸Ð½ÐµÐ½Ð¸Ð¹, ÐºÐ¾ÑÐ¾ÑÑÐµ ÑÐ¾Ð¾ÑÐ²ÐµÑÑÑÐ²ÑÑÑ Ð¿ÑÑÑÐ¼ PARP1, PARP2 Ð¸ BRAF. ÐÑÐ¾Ð¼Ðµ ÑÐ¾Ð³Ð¾, Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ñ in vivo Ð¿ÑÐ¾Ð´ÐµÐ¼Ð¾Ð½ÑÑÑÐ¸ÑÐ¾Ð²Ð°Ð»Ð¸ Ð±Ð¸Ð¾Ð±ÐµÐ·Ð¾Ð¿Ð°ÑÐ½Ð¾ÑÑÑ ÑÐµÑÑÐ¸ÑÑÐµÐ¼ÑÑ ÑÐ¾ÐµÐ´Ð¸Ð½ÐµÐ½Ð¸Ð¹ Ð´Ð»Ñ Ð·Ð´Ð¾ÑÐ¾Ð²ÑÑ Ð¼ÑÑÐµÐ¹ Ð¸ Ð·Ð½Ð°ÑÐ¸ÑÐµÐ»ÑÐ½Ð¾Ðµ Ð¸Ð½Ð³Ð¸Ð±Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ðµ Ð¼ÐµÑÐ°ÑÑÐ°ÑÐ¸ÑÐµÑÐºÐ¸Ñ ÑÐ·Ð»Ð¾Ð² (ÐºÐ¾Ð½ÑÑÐ¾Ð»Ñ = 223 Â± 15 Ð¿Ð¾ ÑÑÐ°Ð²Ð½ÐµÐ½Ð¸Ñ Ñ Ð¼ÑÑÐ°Ð¼Ð¸, Ð¿Ð¾Ð»ÑÑÐ°ÑÑÐ¸Ð¼Ð¸ ÑÐµÑÐ°Ð¿Ð¸Ñ, = 21 Â± 4). ÐÐ¸ÑÑÐ¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÐ¸Ð¹ Ð°Ð½Ð°Ð»Ð¸Ð· Ð½Ðµ Ð²ÑÑÐ²Ð¸Ð» Ð½Ð¸ÐºÐ°ÐºÐ¸Ñ Ð°Ð½Ð¾Ð¼Ð°Ð»ÑÐ½ÑÑ Ð¸Ð·Ð¼ÐµÐ½ÐµÐ½Ð¸Ð¹ Ð² Ð¾ÑÐ½Ð¾Ð²Ð½ÑÑ Ð¾ÑÐ³Ð°Ð½Ð°Ñ (Ð¿ÐµÑÐµÐ½Ð¸, ÑÐµÐ»ÐµÐ·ÐµÐ½ÐºÐµ, Ð¿Ð¾ÑÐºÐ°Ñ Ð¸ ÑÐµÑÐ´ÑÐµ) Ð¿Ð¾ÑÐ»Ðµ ÑÐµÑÐ°Ð¿Ð¸Ð¸. Ð¢Ð°ÐºÐ¸Ð¼ Ð¾Ð±ÑÐ°Ð·Ð¾Ð¼, ÑÐ°Ð·ÑÐ°Ð±Ð¾ÑÐ°Ð½Ð½ÑÐµ ÑÐ¾ÐµÐ´Ð¸Ð½ÐµÐ½Ð¸Ñ Ð´ÐµÐ¼Ð¾Ð½ÑÑÑÐ¸ÑÑÑÑ Ð²ÑÑÐ¾ÐºÑÑ ÑÑÑÐµÐºÑÐ¸Ð²Ð½Ð¾ÑÑÑ Ð¿ÑÐ¸ Ð»ÐµÑÐµÐ½Ð¸Ð¸ Ð¼ÐµÑÐ°ÑÑÐ°ÑÐ¸ÑÐµÑÐºÐ¾Ð¹ Ð¼ÐµÐ»Ð°Ð½Ð¾Ð¼Ñ Ð»ÐµÐ³ÐºÐ¸Ñ Ð¸ Ð¼Ð¾Ð³ÑÑ Ð±ÑÑÑ Ð² Ð´Ð°Ð»ÑÐ½ÐµÐ¹ÑÐµÐ¼ ÑÐµÐºÐ¾Ð¼ÐµÐ½Ð´Ð¾Ð²Ð°Ð½Ñ Ð´Ð»Ñ Ð´ÐµÑÐ°Ð»ÑÐ½ÑÑ Ð´Ð¾ÐºÐ»Ð¸Ð½Ð¸ÑÐµÑÐºÐ¸Ñ Ð¸ ÐºÐ»Ð¸Ð½Ð¸ÑÐµÑÐºÐ¸Ñ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ð¹.
description: The subject of the graduate qualification work is âStudy of the therapeutic potential of new low-molecular-weight anticancer drugs on the example of metastatic lung melanomaâ. This work is devoted to the study of the therapeutic properties of new low molecular weight compounds, which are potentially inhibitors of the main targets in the treatment of melanoma. Although many inhibitors could significantly increase the therapeutic efficiency against malignant neoplasm, only several have been translated into clinics. Therefore, the development of highly potent and. Here, we focus on small molecule inhibitors with a heterocyclic structure due to their advantages, including possibility of large-scale production, simple modification and purification, and high yield of product. Furthermore, we performed in vitro screening analysis using B16-F10 melanoma cells to reveal the most effective candidates for in vivo studies. Molecular docking revealed the predicted mechanism of action for the tested compounds that correspond to PARP1, PARP2 and BRAF pathways. Further, in vivo studies demonstrated the biosafety of the tested compounds to healthy mice and significant inhibition of the metastatic nodules (untreated mice = 223 Â± 15 versus treated mice = 21 Â± 4). Histological analysis detected no abnormal changes in the main organs (the liver, spleen, kidneys, and heart) after the therapy. Thus, the developed compounds demonstrate high efficiency in the treatment of pulmonary metastatic melanoma and can be further recommended for detailed preclinical and clinical studies.