Acrizanib is an orally active vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor. Acrizanib blocks the angiogenesis signaling pathway by inhibiting the phosphorylation of VEGFR2. Acrizanib is applicable in research related to age-related macular degeneration and fundus neovascular diseases[1-2].
In vitro, Acrizanib (0-200nM) was used to treat human umbilical vein endothelial cells (HUVECs) stimulated with vascular endothelial growth factor (VEGF, 10ng/mL) for 24 hours. Acrizanib significantly inhibited VEGF-induced cell proliferation, migration, and tube formation ability[3]. After incubating BaF3-Tel-KDR cells with Acrizanib (17.4nM) for 72 hours, Acrizanib significantly inhibited cell proliferation[4].
In vivo, Acrizanib (0.5μL, 10μM solution intravitreal injection) was used to treat a mouse model of oxygen-induced retinopathy. Acrizanib significantly reduced pathological retinal neovascularization[3]. In a laser-induced choroidal neovascularization (CNV) model in Brown Norway rats, Acrizanib (4μL of 1% suspension/eye; three times daily; for 6 days) was administered. Acrizanib significantly inhibited the area of choroidal neovascularization[4].
References:
[1] Al-Khersan H, Hussain RM, Ciulla TA, et al. Innovative therapies for neovascular age-related macular degeneration. Expert Opin Pharmacother. 2019 Oct;20(15):1879-1891.
[2] Hussain RM, Ciulla TA. Emerging vascular endothelial growth factor antagonists to treat neovascular age-related macular degeneration. Expert Opin Emerg Drugs. 2017 Sep;22(3):235-246.
[3] Tang X, Cui K, Wu P, et al. Acrizanib as a Novel Therapeutic Agent for Fundus Neovascularization via Inhibitory Phosphorylation of VEGFR2. Transl Vis Sci Technol. 2024 Jan 2;13(1):1.
[4] Adams CM, Anderson K, Artman G 3rd, et al. The Discovery of N-(1-Methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-((6- ((methylamino)methyl)pyrimidin-4-yl)oxy)-1H-indole-1-carboxamide (Acrizanib), a VEGFR-2 Inhibitor Specifically Designed for Topical Ocular Delivery, as a Therapy for Neovascular Age-Related Macular Degeneration. J Med Chem. 2018 Feb 22;61(4):1622-1635.
Acrizanib是一种具有口服活性的血管内皮生长因子受体2（VEGFR-2）抑制剂。Acrizanib可通过抑制VEGFR2的磷酸化来阻断血管生成信号通路。Acrizanib可用于年龄相关性黄斑变性和眼底新生血管性疾病的相关研究[1-2]。
在体外，Acrizanib（0-200nM）处理血管内皮生长因子（VEGF，10ng/mL）刺激的人脐静脉内皮细胞（HUVECs）24小时，Acrizanib可显著抑制VEGF诱导的细胞增殖、迁移及管形成能力[3]。Acrizanib（17.4nM）孵育BaF3-Tel-KDR细胞72小时，Acrizanib可显著抑制的细胞增殖[4]。
在体内，Acrizanib（0.5μL，10μM溶液玻璃体内注射）用于处理氧诱导视网膜病变小鼠模型。Acrizanib显著减少了病理性视网膜新生血管形成[3]。Acrizanib（4μL 1%混悬液/眼；每日三次；持续6天）用于处理激光诱导的Brown Norway大鼠脉络膜新生血管（CNV）模型。Acrizanib显著抑制了脉络膜新生血管面积[4]。