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靶向血管内皮生长因子受体 2（VEGFR-2）：合成策略的最新见解。

Targeting Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2): Latest Insights on Synthetic Strategies.

机构信息

LAQV-REQUIMTE, Institute for Research and Advanced Training, University of Évora, Rua Romão Ramalho, 59, 7000-641 Evora, Portugal.

Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health & Science, Campus Universitátio, Quinta da Granja, Monte da Caparica, 2829-511 Caparica, Portugal.

出版信息

Molecules. 2024 Nov 13;29(22):5341. doi: 10.3390/molecules29225341.

DOI:10.3390/molecules29225341
PMID:39598729
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11596329/
Abstract

Vascular endothelial growth factor receptor 2 (VEGFR-2) is a crucial mediator of angiogenesis, playing a pivotal role in both normal physiological processes and cancer progression. Tumors harness VEGFR-2 signaling to promote abnormal blood vessel growth, which is a key step in the metastasis process, making it a valuable target for anticancer drug development. While there are VEGFR-2 inhibitors approved for therapeutic use, they face challenges like drug resistance, off-target effects, and adverse side effects, limiting their effectiveness. The quest for new drug candidates with VEGFR-2 inhibitory activity often starts with the selection of key structural motifs present in molecules currently used in clinical practice, expanding the chemical space by generating novel derivatives bearing one or more of these moieties. This review provides an overview of recent advances in the development of novel VEGFR-2 inhibitors, focusing on the synthesis of new drug candidates with promising antiproliferative and VEGFR-2 inhibition activities, organizing them by relevant structural features.

摘要

血管内皮生长因子受体 2（VEGFR-2）是血管生成的关键介质，在正常生理过程和癌症进展中都起着关键作用。肿瘤利用 VEGFR-2 信号通路促进异常血管生长，这是转移过程中的关键步骤，使其成为抗癌药物开发的有价值的靶点。虽然有一些 VEGFR-2 抑制剂被批准用于治疗，但它们面临着耐药性、脱靶效应和不良反应等挑战，限制了它们的有效性。具有 VEGFR-2 抑制活性的新药候选物的探索通常从选择目前临床应用的分子中存在的关键结构基序开始，通过生成带有一个或多个这些部分的新型衍生物来扩展化学空间。本综述概述了新型 VEGFR-2 抑制剂的最新研究进展，重点介绍了具有有前途的抗增殖和 VEGFR-2 抑制活性的新型药物候选物的合成，根据相关结构特征对它们进行了分类。

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