| Identification | Back Directory | [Name]
Aflibercept | [CAS]
862111-32-8 | [Synonyms]
VEGF trap
VEGF Trap R1R2
Aflibercept iso-osmotic ophthalmic | [Molecular Formula]
C4318H6788N1164O1304S32 |
| Hazard Information | Back Directory | [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 (KD=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
(KD=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 36.4?mg/kg | | Administration: | Intravenous injection; 18.2 mg/kg and 36.4?mg/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 |
|
| Company Name: |
LGM Pharma
|
| Tel: |
1-(800)-881-8210 |
| Website: |
www.lgmpharma.com |
| Company Name: |
BOC Sciences
|
| Tel: |
1-631-485-4226; 16314854226 |
| Website: |
https://www.bocsci.com |
| Company Name: |
DC Chemicals
|
| Tel: |
021-58447131 13564518121 |
| Website: |
http://m.is0513.com/ShowSupplierProductsList927327/0.htm |
| Company Name: |
Biolab Reagents
|
| Tel: |
18108604356 18108604356 |
| Website: |
www.biolabreagent.com/ |
|