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.