General Information of Binding Target of SBP (BTS) (ID: ST00059)
BTS Name
Vascular endothelial growth factor A
Synonyms
VEGF-A; Vascular permeability factor; VPF
BTS Type
Protein
Family
PDGF/VEGF growth factor family
Gene Name
VEGFA
Organism
Homo sapiens (Human)
Function
Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth. Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development (By similarity).
UniProt ID
P15692
UniProt Entry
VEGFA_HUMAN
PFam
PF00341 ; PF14554
Gene ID
7422
Sequence
MNFLLSWVHWSLALLLYLHHAKWSQAAPMAEGGGQNHHEVVKFMDVYQRSYCHPIETLVD
IFQEYPDEIEYIFKPSCVPLMRCGGCCNDEGLECVPTEESNITMQIMRIKPHQGQHIGEM
SFLQHNKCECRPKKDRARQEKKSVRGKGKGQKRKRKKSRYKSWSVYVGARCCLMPWSLPG
PHPCGPCSERRKHLFVQDPQTCKCSCKNTDSRCKARQLELNERTCRCDKPRR
Sequence Length
232
Synthetic Binding Protein (SBP) Targeting This BTS
SBP Name Highest Status Mechanism Affinity Application Details Ref
Anticalin Angiocal Phase I Inhibitor Kd: 0.025 nM Solid tumour/cancer [ICD-11: 2A00-2F9Z]
SBP Info
[1], [2], [3]
Cyclotide anti-VEGF-A Research Inhibitor N.A. Cancers [ICD-11: 2D4Z]; Rheumatoid arthritis [ICD-11: FA20.Z]
SBP Info
[4]
DARPin Abicipar pegol Preregistration Inhibitor Kd: 0.002 nM Age related macular degeneration [ICD-11: 9B75.0Z]; Diabetic macular oedema [ICD-11: 9B71.02]
SBP Info
[5], [1], [6]
DARPin anti-PDGF-B/VEGF-A MP0260 Research Inhibitor N.A. Age related macular degeneration [ICD-11: 9B75.0Z]
SBP Info
[7]
DARPin anti-VEGF-A clone 1 Research Antagonist Kd: >=0.025 nM Anti-angiogenic agents for topical and intravitreal applications
SBP Info
[8]
DARPin anti-VEGF-A clone 10 Research Antagonist Kd: >=0.025 nM Anti-angiogenic agents for topical and intravitreal applications
SBP Info
[8]
DARPin anti-VEGF-A clone 2 Research Antagonist Kd: >=0.025 nM Anti-angiogenic agents for topical and intravitreal applications
SBP Info
[8]
DARPin anti-VEGF-A clone 3 Research Antagonist Kd: >=0.025 nM Anti-angiogenic agents for topical and intravitreal applications
SBP Info
[8]
DARPin anti-VEGF-A clone 4 Research Antagonist Kd: >=0.025 nM Anti-angiogenic agents for topical and intravitreal applications
SBP Info
[8]
DARPin anti-VEGF-A clone 5 Research Antagonist Kd: >=0.025 nM Anti-angiogenic agents for topical and intravitreal applications
SBP Info
[8]
DARPin anti-VEGF-A clone 6 Research Antagonist Kd: >=0.025 nM Anti-angiogenic agents for topical and intravitreal applications
SBP Info
[8]
DARPin anti-VEGF-A clone 7 Research Antagonist Kd: >=0.025 nM Anti-angiogenic agents for topical and intravitreal applications
SBP Info
[8]
DARPin anti-VEGF-A clone 8 Research Antagonist Kd: >=0.025 nM Anti-angiogenic agents for topical and intravitreal applications
SBP Info
[8]
DARPin anti-VEGF-A clone 9 Research Antagonist Kd: >=0.025 nM Anti-angiogenic agents for topical and intravitreal applications
SBP Info
[8]
DARPin MP0250 Phase II Antagonist Kd: <1 nM Multiple myeloma [ICD-11: 2A83.Y]; Non-small cell lung cancer [ICD-11: 2C25.Y]; Solid tumour/cancer [ICD-11: 2A00-2F9Z]
SBP Info
[9], [10], [11]
Fab anti-VEGF A4.6.1 Research Binder N.A. Research tool
SBP Info
[12]
Fab anti-VEGF Fab A1 Research Binder Kd: 300 nM Research tool
SBP Info
[13]
Fab anti-VEGF Fab B1 Research Binder Kd: 30 nM Research tool
SBP Info
[13]
Fab anti-VEGF Fab C1 Research Binder Kd: 9.7 nM Research tool
SBP Info
[13]
Fab anti-VEGF Fab D1 Research Binder Kd: 7.8 nM Research tool
SBP Info
[13]
Fab anti-VEGF Fab D2 Research Binder Kd: 4.4 nM Research tool
SBP Info
[13]
Fab anti-VEGF hu2.0 Research Binder Kd: 260 nM Research tool
SBP Info
[12]
Fab anti-VEGF hu2.10 Research Binder Kd: 55 nM Research tool
SBP Info
[12]
Fab anti-VEGF YADS1 Research Binder Kd: 1.8 nM Research tool
SBP Info
[14]
Fab anti-VEGF YADS2 Research Binder Kd: 10 nM Research tool
SBP Info
[14]
Fab anti-VEGF YADS3 Research Binder Kd: 2 nM Research tool
SBP Info
[14]
Fab Ranibizumab Marketed Inhibitor N.A. Choroidal neovascularisation [ICD-11: 9B76]; Degenerative high myopia [ICD-11: 9B76]; Diabetic macular oedema [ICD-11: 9B71.02]; Retinal oedema [ICD-11: 9B78.7]; Age related macular degeneration [ICD-11: 9B75.0Z]; Diabetic retinopathy [ICD-11: 9B71.0]; Retinopathy of prematurity [ICD-11: 9B71.3]; Polypoidal choroidal vasculopathy [ICD-11: 9B75.Y]
SBP Info
[15]
Nanobody anti-VEGF Research Inhibitor N.A. Cancers [ICD-11: 2D4Z]
SBP Info
[16]
Nanobody anti-VEGF clone 22 Research Binder Kd: 10 nM Cancers [ICD-11: 2D4Z]
SBP Info
[17]
Nanobody anti-VEGF clone 23 Research Inhibitor Kd: 10 nM Cancers [ICD-11: 2D4Z]
SBP Info
[17]
Nanobody anti-VEGF clone 35 Research Inhibitor Kd: 45 nM Cancers [ICD-11: 2D4Z]
SBP Info
[17]
Nanobody anti-VEGF clone 42 Research Inhibitor Kd: 60 nM Cancers [ICD-11: 2D4Z]
SBP Info
[17]
Repebody anti-VEGF r-C2 Research Inhibitor Kd: 10.6 nM Age related macular degeneration [ICD-11: 9B75.0Z]; Diabetic retinopathy [ICD-11: 9B71.0Z]; Cancer metastasis [ICD-11: 2E2Z]
SBP Info
[18]
Repebody anti-VEGF r-F1 Research Inhibitor Kd: 80.4 nM Age related macular degeneration [ICD-11: 9B75.0Z]; Diabetic retinopathy [ICD-11: 9B71.0Z]; Cancer metastasis [ICD-11: 2E2Z]
SBP Info
[18]
scFv anti-VEGF-A Brolucizumab Research Binder N.A. Diabetic macular oedema [ICD-11: 9B71.02]; Retinal vein occlusion [ICD-11: 9B74.1]; Diabetic retinopathy [ICD-11: 9B71.0Z]
SBP Info
[19]
scFv anti-VEGF/SasA variants Research Binder N.A. Research tool
SBP Info
[20]
References
1 In vitro-engineered non-antibody protein therapeutics. Protein Cell. 2018 Jan;9(1):3-14.
2 Recent advances in the development of novel protein scaffolds based therapeutics. Int J Biol Macromol. 2017 Sep;102:630-641.
3 Functional characterization of a VEGF-A-targeting Anticalin, prototype of a novel therapeutic human protein class. Angiogenesis. 2016 Jan;19(1):79-94.
4 Engineering stabilized vascular endothelial growth factor-A antagonists: synthesis, structural characterization, and bioactivity of grafted analogues of cyclotides. J Med Chem. 2008 Dec 25;51(24):7697-704.
5 Double-Masked, Randomized, Phase 2 Evaluation of Abicipar Pegol (an Anti-VEGF DARPin Therapeutic) in Neovascular Age-Related Macular Degeneration. J Ocul Pharmacol Ther. 2018 Dec;34(10):700-709.
6 A Mechanistic and Translational Pharmacokinetic-Pharmacodynamic Model of Abicipar Pegol and Vascular Endothelial Growth Factor Inhibition. J Pharmacol Exp Ther. 2020 May;373(2):184-192.
7 Molecular Partners. Product Development Pipeline. 2021.
8 Highly potent VEGF-A-antagonistic DARPins as anti-angiogenic agents for topical and intravitreal applications. Angiogenesis. 2013 Jan;16(1):101-11.
9 DARPins: Promising Scaffolds for Theranostics. Acta Naturae. Oct-Dec 2019;11(4):42-53.
10 MP0250, a VEGF and HGF neutralizing DARPin ? molecule shows high anti-tumor efficacy in mouse xenograft and patient-derived tumor models. Oncotarget. 2017 Oct 11;8(58):98371-98383.
11 Beyond antibodies: ankyrins and DARPins. From basic research to drug approval. Curr Opin Pharmacol . 2020 Apr;51:93-101.
12 Antibody humanization using monovalent phage display. J Biol Chem. 1997 Apr 18;272(16):10678-84.
13 High-throughput generation of synthetic antibodies from highly functional minimalist phage-displayed libraries. J Mol Biol. 2007 Nov 2;373(4):924-40.
14 Synthetic antibodies from a four-amino-acid code: a dominant role for tyrosine in antigen recognition. Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12467-72.
15 Five-Year Outcomes of Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA Ophthalmol. 2018 Oct 1;136(10):1138-1148.
16 A nanobody-derived mimotope against VEGF inhibits cancer angiogenesis. J Enzyme Inhib Med Chem. 2020 Dec;35(1):1233-1239.
17 Inhibition of angiogenesis in human endothelial cell using VEGF specific nanobody. Mol Immunol. 2015 May;65(1):58-67.
18 Anti-Human VEGF Repebody Effectively Suppresses Choroidal Neovascularization and Vascular Leakage. PLoS One. 2016 Mar 25;11(3):e0152522.
19 Brolucizumab: First Approval. Drugs. 2019 Dec;79(18):1997-2000.
20 Antibody variable domain interface and framework sequence requirements for stability and function by high-throughput experiments. Structure. 2014 Jan 7;22(1):22-34.