Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTOHSBA)

• DTT Name: Vascular endothelial growth factor A (VEGFA)
• Synonyms: Vascular permeability factor; VPF; VEGF-A; VEGF
• Gene Name: VEGFA
• DTT Type: Successful target; [1]
• Related Disease:
  Colorectal cancer [ICD-11: 2B91]
  Retinopathy [ICD-11: 9B71]
  Vascular system developmental anomaly [ICD-11: LA90]
• BioChemical Class: Growth factor
• UniProt ID: VEGFA_HUMAN
• TTD ID: T20761
• Sequence:
  MNFLLSWVHWSLALLLYLHHAKWSQAAPMAEGGGQNHHEVVKFMDVYQRSYCHPIETLVD
  IFQEYPDEIEYIFKPSCVPLMRCGGCCNDEGLECVPTEESNITMQIMRIKPHQGQHIGEM
  SFLQHNKCECRPKKDRARQEKKSVRGKGKGQKRKRKKSRYKSWSVYVGARCCLMPWSLPG
  PHPCGPCSERRKHLFVQDPQTCKCSCKNTDSRCKARQLELNERTCRCDKPRR
• Function: 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. Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth.
• KEGG Pathway:
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  Cytokine-cytokine receptor interaction (hsa04060)
  HIF-1 signaling pathway (hsa04066)
  mTOR signaling pathway (hsa04150)
  PI3K-Akt signaling pathway (hsa04151)
  VEGF signaling pathway (hsa04370)
  Focal adhesion (hsa04510)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  MicroRNAs in cancer (hsa05206)
  Renal cell carcinoma (hsa05211)
  Pancreatic cancer (hsa05212)
  Bladder cancer (hsa05219)
  Rheumatoid arthritis (hsa05323)
• Reactome Pathway:
  Regulation of gene expression by Hypoxia-inducible Factor (R-HSA-1234158)
  VEGF ligand-receptor interactions (R-HSA-194313)
  VEGF binds to VEGFR leading to receptor dimerization (R-HSA-195399)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aflibercept	DMT3D5I	Metastatic colorectal cancer	2B91	Approved	[1]
Bevacizumab	DMSD1UN	Metastatic colorectal cancer	2B91	Approved	[2]
Brolucizumab	DMW8QNG	Wet age-related macular degeneration	9B78.3Z	Approved	[3]
Ranibizumab	DMSYPNW	Hereditary hemorrhagic telangiectasia	LA90.00	Approved	[4]

16 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Avastin+/-Tarceva	DMA86FL	Non-small-cell lung cancer	2C25.Y	Phase 3	[5], [6]
Bevacizumab + Erlotinib	DM0MI81	Metastatic colorectal cancer	2B91	Phase 3	[7]
Bevacizumab + Rituximab	DM9EXGI	Lymphoma	2A80-2A86	Phase 3	[7]
Bevacizumab + Trastuzumab	DM9CEI5	Breast cancer	2C60-2C65	Phase 3	[7]
Faricimab	DM83SEB	Diabetic macular edema	9B71.02	Phase 3	[8]
Abicipar pegol	DM59OJ2	Diabetic macular edema	9B71.02	Phase 2	[9]
PTC299	DMP9TKE	Rheumatoid arthritis	FA20	Phase 2	[10]
RG7221	DM8J9DC	Colorectal cancer	2B91.Z	Phase 2	[11]
RO5520985	DMD3WNP	Colorectal cancer	2B91.Z	Phase 2	[12]
MP0250	DMR3VCY	Non-small-cell lung cancer	2C25.Y	Phase 1/2	[13]
SNN-0029	DMNV8SY	Lateral sclerosis	8B61	Phase 1/2	[14]
ABI-011	DM1KD7U	Lymphoma	2A80-2A86	Phase 1	[13]
AT001/r84	DMD2BIT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[15]
MP-0112	DMJOMD4	Macular degeneration	9B78.3	Phase 1	[16]
Navicixizumab	DMZ2G69	Colorectal cancer	2B91.Z	Phase 1	[17]
SFLT-01	DMD2GKF	Macular degeneration	9B78.3	Phase 1	[18]

63 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,6-naphyridine-4-ketone fused heterocyclic derivative 1	DMF6W2Y	N. A.	N. A.	Patented	[19]
3-phenyl-5-ureidoisothiazole-4-carboximide and 3-amino-5-phenylisothiazole derivative 1	DMB1JG2	Blood vessel proliferative disorder	BE2Z	Patented	[19]
Antibodie derivative 1	DMY5J23	N. A.	N. A.	Patented	[19]
Antibodie derivative 11	DMPG3Y8	N. A.	N. A.	Patented	[19]
Antibodie derivative 2	DMU7YC2	N. A.	N. A.	Patented	[19]
Antibodie derivative 3	DMNPBRG	N. A.	N. A.	Patented	[19]
Antibodie derivative 4	DM2WMGO	N. A.	N. A.	Patented	[19]
Antibodie derivative 7	DMJN37O	Solid tumour/cancer	2A00-2F9Z	Patented	[19]
Antibodie derivative 8	DM0CEJM	N. A.	N. A.	Patented	[19]
Antibodie derivative 9	DMDRJ31	Carotid artery disease	8B10	Patented	[19]
Carbamide derivative 14	DMU04PM	N. A.	N. A.	Patented	[19]
Carbamide derivative 15	DM2TDXW	N. A.	N. A.	Patented	[19]
Carbamide derivative 16	DMLPOUR	N. A.	N. A.	Patented	[19]
Carbamide derivative 17	DMUF5AC	N. A.	N. A.	Patented	[19]
Carbamide derivative 18	DMZ37XI	N. A.	N. A.	Patented	[19]
Carbamide derivative 19	DMLDXOB	N. A.	N. A.	Patented	[19]
Carbamide derivative 20	DMYSWG1	N. A.	N. A.	Patented	[19]
Carbamide derivative 21	DMD03J5	N. A.	N. A.	Patented	[19]
Carbamide derivative 22	DMC3TJI	N. A.	N. A.	Patented	[19]
Carbamide derivative 23	DM0IRPO	N. A.	N. A.	Patented	[19]
Conjugated 3-(indolyl)-and 3-(azaindolyl)-4-arylmaleimide compound 1	DMLZMIG	Gastric adenocarcinoma	2B72	Patented	[19]
Indoline derivative 12	DMJURBM	N. A.	N. A.	Patented	[19]
Indoline derivative 13	DM982GD	N. A.	N. A.	Patented	[19]
Indoline derivative 14	DM8DHRN	N. A.	N. A.	Patented	[19]
Indoline derivative 15	DMRFEH4	N. A.	N. A.	Patented	[19]
Indoline derivative 16	DM9AGBT	N. A.	N. A.	Patented	[19]
Indoline derivative 17	DMXSFJ8	N. A.	N. A.	Patented	[19]
Indoline derivative 18	DMX640D	N. A.	N. A.	Patented	[19]
Indoline derivative 19	DMOHITL	N. A.	N. A.	Patented	[19]
Indoline derivative 20	DM4JNLQ	N. A.	N. A.	Patented	[19]
Indoline derivative 21	DM3YPX1	N. A.	N. A.	Patented	[19]
Oxetane 3,3-dicarboxamide compound 1	DMSB09X	Virus infection	1A24-1D9Z	Patented	[19]
Oxetane 3,3-dicarboxamide compound 2	DMMCTAK	Virus infection	1A24-1D9Z	Patented	[19]
PMID28621580-Compound-WO2013036866C66	DMBTZ8I	Solid tumour/cancer	2A00-2F9Z	Patented	[19]
PMID28621580-Compound-WO2013112959C68	DM15OKA	Fibrosis	GA14-GC01	Patented	[19]
PMID28621580-Compound-WO2014079545C69	DMR58TX	N. A.	N. A.	Patented	[19]
PMID28621580-Compound-WO2015089220C70	DMX96FI	Age-related macular degeneration	9B75.0	Patented	[19]
Pyridine derivative 10	DMVL2G3	N. A.	N. A.	Patented	[19]
Pyridine derivative 11	DMF9VMW	N. A.	N. A.	Patented	[19]
Pyridine derivative 2	DMGSUIV	N. A.	N. A.	Patented	[19]
Pyridine derivative 3	DMFALQN	N. A.	N. A.	Patented	[19]
Pyridine derivative 4	DM6N8T3	Solid tumour/cancer	2A00-2F9Z	Patented	[19]
Pyridine derivative 5	DMXP6W1	N. A.	N. A.	Patented	[19]
Pyridine derivative 6	DM8NBM0	N. A.	N. A.	Patented	[19]
Pyridine derivative 7	DMYT1QN	N. A.	N. A.	Patented	[19]
Pyridine derivative 8	DMITVUY	N. A.	N. A.	Patented	[19]
Pyridine derivative 9	DMVF1BI	N. A.	N. A.	Patented	[19]
Pyrimidine derivative 10	DMBEZUY	N. A.	N. A.	Patented	[19]
Pyrimidine derivative 11	DMJ4QD5	N. A.	N. A.	Patented	[19]
Pyrimidine derivative 5	DMNET19	Blood vessel proliferative disorder	BE2Z	Patented	[19]
Pyrimidine derivative 6	DMBAHYO	Blood vessel proliferative disorder	BE2Z	Patented	[19]
Pyrimidine derivative 7	DMF6DUT	Blood vessel proliferative disorder	BE2Z	Patented	[19]
Pyrimidine derivative 8	DMVW25O	N. A.	N. A.	Patented	[19]
Pyrimidine derivative 9	DMV6U9Y	N. A.	N. A.	Patented	[19]
Quinoline and quinazoline derivative 10	DM6E1N4	N. A.	N. A.	Patented	[19]
Quinoline and quinazoline derivative 2	DM9PSI3	N. A.	N. A.	Patented	[19]
Quinoline and quinazoline derivative 3	DMGY4WO	N. A.	N. A.	Patented	[19]
Quinoline and quinazoline derivative 4	DM5VCQP	N. A.	N. A.	Patented	[19]
Quinoline and quinazoline derivative 5	DM7RQ2G	N. A.	N. A.	Patented	[19]
Quinoline and quinazoline derivative 6	DMZ2TB5	N. A.	N. A.	Patented	[19]
Quinoline and quinazoline derivative 7	DMMJEWB	N. A.	N. A.	Patented	[19]
Quinoline and quinazoline derivative 8	DMW3JH0	N. A.	N. A.	Patented	[19]
Quinoline and quinazoline derivative 9	DMBL86O	N. A.	N. A.	Patented	[19]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bevasiranib	DMIEB8Y	Exudative age-related macular degeneration	9B78.3Z	Discontinued in Phase 3	[20]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Lateral sclerosis	8A00.0	Cervical spinal cord	3.61E-01	0.15	0.47
Rectal cancer	2C82	Rectal colon tissue	2.07E-03	1.2	2.26

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] FDA Approved Drug Products from FDA Official Website. 2004. Application Number: (ANDA) 125085.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [4] Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina. 2006 Oct;26(8):859-70.
• [5] Clinical pipeline report, company report or official report of Genentech (2009).
• [6] Clinical pipeline report, company report or official report of Genentech (2009).
• [7] Clinical pipeline report, company report or official report of Roche (2009).
• [8] Faricimab: an investigational agent targeting the Tie-2/angiopoietin pathway and VEGF-A for the treatment of retinal diseases. Expert Opin Investig Drugs. 2021 Mar;30(3):193-200.
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] Phase I and pharmacokinetic trial of PTC299 in pediatric patients with refractory or recurrent central nervous system tumors: a PBTC study.J Neurooncol.2015 Jan;121(1):217-24.
• [11] Bispecific antibodies and their applications
• [12] Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801.
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] Clinical pipeline report, company report or official report of Neuronova.
• [15] Clinical pipeline report, company report or official report of Affitech (2011).
• [16] Treatment of exudative age-related macular degeneration with a designed ankyrin repeat protein that binds vascular endothelial growth factor: a phase I/II study. Am J Ophthalmol. 2014 Oct;158(4):724-732.e2.
• [17] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [18] sFLT01: a novel fusion protein with antiangiogenic activity. Mol Cancer Ther. 2011 Mar;10(3):404-15.
• [19] VEGFR-2 inhibitors and the therapeutic applications thereof: a patent review (2012-2016).Expert Opin Ther Pat. 2017 Sep;27(9):987-1004.
• [20] Bevasiranib for the Treatment of Wet, Age-Related Macular Degeneration