Aflibercept is a high-affinity soluble decoy vascular endothelial growth factor (VEGF) receptor and a potent angiogenesis inhibitor that binds vascular endothelial growth factor and placental growth factor (PlGF) with extremely high affinity. Preclinical studies have shown that Aflibercept has potent antitumor and antiangiogenic activities against a variety of tumors, including melanoma and solid tumors[1].
Aflibercept (7.5μg/ml; 10min) inhibits galectin-1-mediated VEGFR2 activation[2]. Aflibercept (15nM; 1h) does not exhibit significant cell surface binding to ARPE-19 and HUVEC. Aflibercept (500nM; 10-15min) in the presence of heparin was unable to stimulate serotonin release[3].
Aflibercept (10 and 25mg/kg; SC; twice-weekly; 30 days) inhibited primary tumor growth by 74% and 78% and Formation of detectable lung metastases was inhibited in 98% of cases [4] . Aflibercept (10mg/kg; 3h) can reduce stroke-induced VEGF-A and VEGFR2 expression, alleviate brain edema and Blood-Brain Barrier disruption, and improve the survival rate of obese mice after stroke after middle cerebral artery occlusion (MCAO) [5].
References:
[1] Bender J G, Blaney S M, Borinstein S, et al. A phase I trial and pharmacokinetic study of aflibercept (VEGF Trap) in children with refractory solid tumors: a children's oncology group phase I consortium report[J]. Clinical cancer research, 2012, 18(18): 5081-5089.
[2] Kanda A, Noda K, Saito W, Ishida S. Aflibercept Traps Galectin-1, an Angiogenic Factor Associated with Diabetic Retinopathy. Sci Rep. 2015 Dec 9;5:17946.
[3] MacDonald DA, Martin J, Muthusamy KK, Luo JK, Pyles E, Rafique A, Huang T, Potocky T, Liu Y, Cao J, Bono F, Delesque N, Savi P, Francis J, Amirkhosravi A, Meyer T, Romano C, Glinka M, Yancopoulos GD, Stahl N, Wiegand SJ, Papadopoulos N. Aflibercept exhibits VEGF binding stoichiometry distinct from bevacizumab and does not support formation of immune-like complexes. Angiogenesis. 2016 Jul;19(3):389-406.
[4] Moroney JW, Sood AK, Coleman RL. Aflibercept in epithelial ovarian carcinoma. Future Oncol. 2009 Jun;5(5):591-600.
[5] Kim ID, Cave JW, Cho S. Aflibercept, a VEGF (Vascular Endothelial Growth Factor)-Trap, Reduces Vascular Permeability and Stroke-Induced Brain Swelling in Obese Mice. Stroke. 2021 Aug;52(8):2637-2648.
Aflibercept 是一种高亲和力的可溶性诱饵血管内皮生长因子受体（Vascular Endothelial Growth Factor, VEGF）和强效血管生成抑制剂，能以极高的亲和力结合血管内皮生长因子和胎盘生长因子 (PlGF)。临床前研究表明，Aflibercept 对黑色素瘤和实体瘤等多种肿瘤具有强大的抗肿瘤和抗血管生成活性[1]。
Aflibercept（7.5μg/ml；10min）可抑制半乳糖凝集素-1 介导的 VEGFR2 激活[2]。Aflibercept（15nM；1h）与 ARPE-19 和 HUVEC 细胞表面无明显结合。肝素存在下的Aflibercept（500nM；10-15min）无法刺激血清素释放[3]。
Aflibercept（10，25mg/kg；SC；twice-weekly；30d）分别抑制了 74% 和 78%的原发性肿瘤生长，并且在 98% 的病例中抑制了可检测的肺转移形成[4]。Aflibercept（10mg/kg；3h）在大脑中动脉闭塞（MCAO）后可降低中风引起的 VEGF-A 和 VEGFR2 表达，减轻脑水肿和血脑屏障通透性破坏，提高肥胖小鼠中风后生存率[5]。