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Aflibercept

Product NameAflibercept
CAS862111-32-8
MFC4318H6788N1164O1304S32
MW0
EINECS
MOL FileMol File

Chemical Properties

form	Liquid
color	Colorless to light yellow

Safety Information

Hazardous Substances Data

862111-32-8(Hazardous Substances Data)

Usage And Synthesis

Description

In November 2011, the U.S. FDA approved the recombinant fusion protein aflibercept, administered as an intravitreal injection, for the treatment of patients with neovascular (wet) age-related macular degeneration (AMD). Aflibercept differs from these agents in that it acts as a soluble decoy receptor that binds all VEGF isoforms more tightly than their native receptors, thereby diverting VEGF from its normal function. Aflibercept consists of a fusion of the second Ig domain of human VEGF receptor 1 and the third Ig domain of human VEGF receptor 2 fused to the constant region of (Fc) of human immunoglobulin G1. Aflibercept is a dimeric glycoprotein with a protein molecular weight of 97 kDa and glycoside molecular weight of 18 kDa. It is produced in recombinant Chinese hamster ovary (CHO) cells that overexpress the fusion protein. Aflibercept has subpicomolar affinity for VEGF-A (K_D=0.66 pM for VEGF-A₁₆₅ and 0.19 pM for VEGF-A₁₂₁), the major driver of pathological angiogenesis and vascular leak in wet AMD.19 Ranibizumab and bevacizumab bind VEGF-A₁₆₅ with lower affinity (K_D=20.6 and 35.1 pM, respectively).

Originator

Regeneron Pharmaceuticals (United States)

Uses

Aflibercept (VEGF Trap) is a soluble decoy VEGFR constructed by fusing the Ig domains of VEGFR1 and VEGFR2 with the Fc region of human IgG1. Aflibercept inhibits VEGF signaling by reducing VEGF-regulated processes. Aflibercept can be used for thr research of age-related macular degeneration (AMD) and cardiovascular disease[1][2][3].

brand name

Eylea

in vivo

Aflibercept (10 mg/kg; 3 h post-middle cerebral artery occlusion (MCAO)) reduces stroke-induced VEGF-A and VEGFR2 expression, and brain edema, and BBB disruption and improves poststroke survival in obese mice^[2]. Aflibercept (18.2 mg/kg and 36.4 mg/kg; i.v. once) affects BP, ROS and eNOS production in mice^[3].

Animal Model:	Male C57BL/6 mice^[3]
Dosage:	18.2 mg/kg and 36.4mg/kg
Administration:	Intravenous injection; 18.2 mg/kg and 36.4mg/kg once
Result:	Rapidly and dose-dependently elevated BP in mice and markedly impaired endothelial-dependent relaxation (EDR) and resulted in NADPH oxidases 1 (NOX1)- and NADPH oxidases 4 (NOX4)-mediated generation of ROS, decreased the activation of protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) concurrently with a reduction in nitric oxide (NO) production and elevation of ET-1 levels in mouse aortas.

References

[1] Klettner A, et al. Effects of aflibercept on primary RPE cells: toxicity, wound healing, uptake and phagocytosis. Br J Ophthalmol. 2014 Oct;98(10):1448-52. DOI:10.1136/bjophthalmol-2014-305105
[2] Kim ID, et al. 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. DOI:10.1161/STROKEAHA.121.034362
[3] Dong ZC, et al. The vascular endothelial growth factor trap aflibercept induces vascular dysfunction and hypertension via attenuation of eNOS/NO signaling in mice. Acta Pharmacol Sin. 2021 Sep;42(9):1437-1448. DOI:10.1038/s41401-020-00569-1

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