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Molecule Details

General Information of the Molecule
Name
Vascular endothelial growth factor A (VEGFA)
Synonyms
Vascular permeability factor; VPF; VEGF-A; VEGF
Gene Name
VEGFA
Gene ID
7422
Sequence
MNFLLSWVHWSLALLLYLHHAKWSQAAPMAEGGGQNHHEVVKFMDVYQRSYCHPIETLVD
IFQEYPDEIEYIFKPSCVPLMRCGGCCNDEGLECVPTEESNITMQIMRIKPHQGQHIGEM
SFLQHNKCECRPKKDRARQEKKSVRGKGKGQKRKRKKSRYKSWSVYVGARCCLMPWSLPG
PHPCGPCSERRKHLFVQDPQTCKCSCKNTDSRCKARQLELNERTCRCDKPRR
    Click to Show/Hide
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.
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Uniprot ID
VEGFA_HUMAN
Pfam
PF00341 ; PF14554
KEGG ID
hsa7422
TTD ID
T20761
A List of Drug Combination(s) Able to Regulate This Molecule
          Expression Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Expression of This Molecule [1]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Genistein   NP Info  + N-(4-hydroxyphenyl) retinamide   Drug Info 
                    Structure +
                    Drug Combination 2 Down-regulating the Expression of This Molecule [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Pterostilbene   NP Info  + Vorinostat   Drug Info 
                    Structure +
                    Drug Combination 3 Down-regulating the Expression of This Molecule [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 4 Down-regulating the Expression of This Molecule [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Ellagic acid   NP Info  + Temozolomide   Drug Info 
                    Structure +
                    Drug Combination 5 Down-regulating the Expression of This Molecule [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Schisandrol B   NP Info  + Doxorubicin   Drug Info 
                    Structure +
                    Drug Combination 6 Down-regulating the Expression of This Molecule [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Thymoquinone   NP Info  + Bortezomib   Drug Info 
                    Structure +
                    Drug Combination 7 Down-regulating the Expression of This Molecule [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Celecoxib   Drug Info 
                    Structure +
                    Drug Combination 8 Down-regulating the Expression of This Molecule [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Triptolide   NP Info  + AMD3100   Drug Info 
                    Structure +
                    Drug Combination 9 Down-regulating the Expression of This Molecule [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Honokiol   NP Info  + Celecoxib   Drug Info 
                    Structure +
                    Drug Combination 10 Down-regulating the Expression of This Molecule [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Epigallocatechin gallate   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 11 Down-regulating the Expression of This Molecule [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Ursolic acid   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 12 Down-regulating the Expression of This Molecule [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Triptolide   NP Info  + 5-LOX shRNA   Drug Info 
                    Structure +
                    Drug Combination 13 Down-regulating the Expression of This Molecule [13]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Capecitabine   Drug Info 
                    Structure +
                    Drug Combination 14 Down-regulating the Expression of This Molecule [14]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Epigallocatechin gallate   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 15 Down-regulating the Expression of This Molecule [15]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Apigenin   NP Info  + HA14-1   Drug Info 
                    Structure +
                    Drug Combination 16 Down-regulating the Expression of This Molecule [16]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Ginsenoside Rg3   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 17 Down-regulating the Expression of This Molecule [17]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Pinocembrin   NP Info  + Simvastatin   Drug Info 
                    Structure +
                    Drug Combination 18 Down-regulating the Expression of This Molecule [18]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Quercetin   NP Info  + 2-methoxyestradiol   Drug Info 
                    Structure +
                    Drug Combination 19 Down-regulating the Expression of This Molecule [19]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Epigallocatechin gallate   NP Info  + Celecoxib   Drug Info 
                    Structure +
                    Drug Combination 20 Down-regulating the Expression of This Molecule [20]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Gambogic acid   NP Info  + Sunitinib   Drug Info 
                    Structure +
                    Drug Combination 21 Down-regulating the Expression of This Molecule [21]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Ginsenoside Rg3   NP Info  + Endostar   Drug Info 
                    Structure +
                    Drug Combination 22 Down-regulating the Expression of This Molecule [22]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 23 Down-regulating the Expression of This Molecule [23]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 24 Down-regulating the Expression of This Molecule [24]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Noscapine   NP Info  + Doxorubicin   Drug Info 
                    Structure +
                    Drug Combination 25 Down-regulating the Expression of This Molecule [25]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Epigallocatechin gallate   NP Info  + SU5416   Drug Info 
                    Structure +
                    Drug Combination 26 Down-regulating the Expression of This Molecule [26]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Noscapine   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 27 Down-regulating the Expression of This Molecule [27]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Cordycepin   NP Info  + Apatinib   Drug Info 
                    Structure +
                    Drug Combination 28 Down-regulating the Expression of This Molecule [28]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Shikonin   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 29 Down-regulating the Expression of This Molecule [29]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + TNF-related apoptosis inducing ligand    Drug Info 
                    Structure +
                    Drug Combination 30 Down-regulating the Expression of This Molecule [30]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Ursolic acid   NP Info  + Capecitabine   Drug Info 
                    Structure +
                    Drug Combination 31 Down-regulating the Expression of This Molecule [31]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Ginsenoside Rg3   NP Info  + Cyclophosphamide   Drug Info 
                    Structure +
                    Drug Combination 32 Down-regulating the Expression of This Molecule [32]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Thymoquinone   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 33 Down-regulating the Expression of This Molecule [33]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Ginsenoside Rg3   NP Info  + Capecitabine   Drug Info 
                    Structure +
                    Drug Combination 34 Down-regulating the Expression of This Molecule [34]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Allyl isothiocyanate   NP Info  + Celecoxib   Drug Info 
                    Structure +
                    Drug Combination 35 Down-regulating the Expression of This Molecule [35]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Sorafenib   Drug Info 
                    Structure +
                    Drug Combination 36 Down-regulating the Expression of This Molecule [36]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Tetrandrine   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 37 Down-regulating the Expression of This Molecule [37]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Bacillus Calmette-Guerin   Drug Info 
                    Structure +
                    Drug Combination 38 Down-regulating the Expression of This Molecule [38]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Thalidomide   Drug Info 
                    Structure +
                 Up-regulation     Click to Show/Hide
                    Drug Combination 1 Up-regulating the Expression of This Molecule [39]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Exemestane + Triptorelin + Cisplatin
    Click to Show/Hide the Each NP or Drug Structure of This Combination
Exemestane   NP Info     Drug Info 
   Drug Info 
                    Drug Combination 2 Up-regulating the Expression of This Molecule [40]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + PX-478   Drug Info 
                    Structure +
                    Drug Combination 3 Up-regulating the Expression of This Molecule [41]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Artesunate   NP Info  + Tetramethylpyrazine   Drug Info 
                    Structure +
Natural Product(s) of This Target
1 Polydatin  NP Info  Investigative Polygonum cuspidatum
2 Wogonoside  NP Info  Investigative Scutellaria baicalensis
Drug(s) of This Target
1 25-methoxyl-dammarane-3beta, 12beta, 20-triol  Drug Info  Investigative Breast cancer
2 Bevacizumab  Drug Info  Approved Colorectal cancer
References
Reference 1 Combination of N-(4-hydroxyphenyl) retinamide and genistein increased apoptosis in neuroblastoma SK-N-BE2 and SH-SY5Y xenografts. Neuroscience. 2009 Sep 29;163(1):286-95.
Reference 2 Targeting MTA1/HIF-1Alpha signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression. Cancer Med. 2017 Nov;6(11):2673-2685.
Reference 3 Effect of resveratrol and in combination with 5-FU on murine liver cancer. World J Gastroenterol. 2004 Oct 15;10(20):3048-52.
Reference 4 Combining Ellagic Acid with Temozolomide Mediates the Cadherin Switch and Angiogenesis in a Glioblastoma Model. World Neurosurg. 2019 Dec;132:e178-e184.
Reference 5 Enhanced antitumour efficacy of functionalized doxorubicin plus schisandrin B co-delivery liposomes via inhibiting epithelial-mesenchymal transition. J Liposome Res. 2021 Jun;31(2):113-129.
Reference 6 Thymoquinone overcomes chemoresistance and enhances the anticancer effects of bortezomib through abrogation of NF-KappaB regulated gene products in multiple myeloma xenograft mouse model. Oncotarget. 2014 Feb 15;5(3):634-48.
Reference 7 Celecoxib and curcumin synergistically inhibit the growth of colorectal cancer cells. Clin Cancer Res. 2005 Sep 15;11(18):6738-44.
Reference 8 AMD3100 combined with triptolide inhibit proliferation, invasion and metastasis and induce apoptosis of human U2OS osteosarcoma cells. Biomed Pharmacother. 2017 Feb;86:677-685.
Reference 9 Tuning mPEG-PLA/vitamin E-TPGS-based mixed micelles for combined celecoxib/honokiol therapy for breast cancer. Eur J Pharm Sci. 2020 Apr 15;146:105277.
Reference 10 Reversal of 5-fluorouracil resistance by EGCG is mediate by inactivation of TFAP2A/VEGF signaling pathway and down-regulation of MDR-1 and P-gp expression in gastric cancer. Oncotarget. 2017 Sep 6;8(47):82842-82853.
Reference 11 Ursolic acid inhibits the growth of human pancreatic cancer and enhances the antitumor potential of gemcitabine in an orthotopic mouse model through suppression of the inflammatory microenvironment. Oncotarget. 2016 Mar 15;7(11):13182-96.
Reference 12 Triptolide augments the effects of 5-lipoxygenase RNA interference in suppressing pancreatic tumor growth in a xenograft mouse model. Cancer Chemother Pharmacol. 2012 Jan;69(1):253-61.
Reference 13 Curcumin sensitizes human colorectal cancer to capecitabine by modulation of cyclin D1, COX-2, MMP-9, VEGF and CXCR4 expression in an orthotopic mouse model. Int J Cancer. 2009 Nov 1;125(9):2187-97.
Reference 14 Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis. Oncogene. 2008 Mar 27;27(14):2055-63.
Reference 15 Bcl-2 inhibitor and apigenin worked synergistically in human malignant neuroblastoma cell lines and increased apoptosis with activation of extrinsic and intrinsic pathways. Biochem Biophys Res Commun. 2009 Oct 30;388(4):705-10.
Reference 16 Inhibitory effect of ginsenoside Rg3 combined with gemcitabine on angiogenesis and growth of lung cancer in mice. BMC Cancer. 2009 Jul 23;9:250.
Reference 17 Inhibitory effect of the combination therapy of simvastatin and pinocembrin on atherosclerosis in ApoE-deficient mice. Lipids Health Dis. 2012 Dec 5;11:166.
Reference 18 Combination of Quercetin and 2-Methoxyestradiol Enhances Inhibition of Human Prostate Cancer LNCaP and PC-3 Cells Xenograft Tumor Growth. PLoS One. 2015 May 26;10(5):e0128277.
Reference 19 (-)-Epigallocatechin-3-gallate, a green tea-derived catechin, synergizes with celecoxib to inhibit IL-1-induced tumorigenic mediators by human pancreatic adenocarcinoma cells Colo357. Eur J Pharmacol. 2012 Jun 5;684(1-3):36-43.
Reference 20 Targeting renal cell carcinoma with gambogic acid in combination with sunitinib in vitro and in vivo. Asian Pac J Cancer Prev. 2012;13(12):6463-8.
Reference 21 Inhibiting effect of Endostar combined with ginsenoside Rg3 on breast cancer tumor growth in tumor-bearing mice. Asian Pac J Trop Med. 2016 Feb;9(2):180-3.
Reference 22 Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res. 2007 Apr 15;67(8):3853-61.
Reference 23 Resveratrol, a multitargeted agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer. Int J Cancer. 2010 Jul 15;127(2):257-68.
Reference 24 Antitumor activity of Noscapine in combination with Doxorubicin in triple negative breast cancer. PLoS One. 2011 Mar 15;6(3):e17733.
Reference 25 SU5416 and EGCG work synergistically and inhibit angiogenic and survival factors and induce cell cycle arrest to promote apoptosis in human malignant neuroblastoma SH-SY5Y and SK-N-BE2 cells. Neurochem Res. 2011 Aug;36(8):1383-96.
Reference 26 Enhanced anticancer activity of gemcitabine in combination with noscapine via antiangiogenic and apoptotic pathway against non-small cell lung cancer. PLoS One. 2011;6(11):e27394.
Reference 27 Combination of Cordycepin and Apatinib Synergistically Inhibits NSCLC Cells by Down-Regulating VEGF/PI3K/Akt Signaling Pathway. Front Oncol. 2020 Sep 7;10:1732.
Reference 28 Shikonin suppresses tumor growth and synergizes with gemcitabine in a pancreatic cancer xenograft model: Involvement of NF-kappaB signaling pathway. Biochem Pharmacol. 2014 Apr 1;88(3):322-33.
Reference 29 Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5). Carcinogenesis. 2005 Nov;26(11):1905-13.
Reference 30 Ursolic acid inhibits growth and metastasis of human colorectal cancer in an orthotopic nude mouse model by targeting multiple cell signaling pathways: chemosensitization with capecitabine. Clin Cancer Res. 2012 Sep 15;18(18):4942-53.
Reference 31 Antiangiogenic effect of low-dose cyclophosphamide combined with ginsenoside Rg3 on Lewis lung carcinoma. Biochem Biophys Res Commun. 2006 Apr 14;342(3):824-8.
Reference 32 Thymoquinone subdues tumor growth and potentiates the chemopreventive effect of 5-fluorouracil on the early stages of colorectal carcinogenesis in rats. Drug Des Devel Ther. 2016 Jul 11;10:2239-53.
Reference 33 Antiangiogenic effect of capecitabine combined with ginsenoside Rg3 on breast cancer in mice. Cancer Biother Radiopharm. 2008 Oct;23(5):647-53.
Reference 34 Enhanced inhibition of urinary bladder cancer growth and muscle invasion by allyl isothiocyanate and celecoxib in combination. Carcinogenesis. 2013 Nov;34(11):2593-9.
Reference 35 [Inhibitory effect of sorafenib combined with arsenic trioxide on hepatocellular carcinoma cells]. Nan Fang Yi Ke Da Xue Xue Bao. 2008 Apr;28(4):639-41.
Reference 36 Combination of Tetrandrine with cisplatin enhances cytotoxicity through growth suppression and apoptosis in ovarian cancer in vitro and in vivo. Cancer Lett. 2011 May 1;304(1):21-32.
Reference 37 Curcumin potentiates the antitumor effects of Bacillus Calmette-Guerin against bladder cancer through the downregulation of NF-kappaB and upregulation of TRAIL receptors. Cancer Res. 2009 Dec 1;69(23):8958-66.
Reference 38 Inhibitory Effects of Arsenic Trioxide and Thalidomide on Angiogenesis and Vascular Endothelial Growth Factor Expression in Leukemia Cells. Asian Pac J Cancer Prev. 2018 Apr 27;19(4):1127-1134.
Reference 39 The antitumor efficacy of cisplatin in combination with triptorelin and exemestane therapy for an ovarian cancer ascites model in Wistar rats. Exp Oncol. 2015 Mar;37(1):30-5.
Reference 40 Arsenic trioxide plus PX-478 achieves effective treatment in pancreatic ductal adenocarcinoma. Cancer Lett. 2016 Aug 10;378(2):87-96.
Reference 41 Synergistic Effect of Combined Artesunate and Tetramethylpyrazine in Experimental Cerebral Malaria. ACS Infect Dis. 2020 Sep 11;6(9):2400-2409.
Reference 42 Polydatin suppresses VEGF-induced angiogenesis through binding with VEGF and inhibiting its receptor signaling. FASEB J. 2019 Jan;33(1):532-544.
Reference 43 A Systems Pharmacology Approach Uncovers Wogonoside as an Angiogenesis Inhibitor of Triple-Negative Breast Cancer by Targeting Hedgehog Signaling. Cell Chem Biol. 2019 Aug 15;26(8):1143-1158.e6.
Reference 44 Novel anti-inflammatory properties of the angiogenesis inhibitor vasostatin. J Invest Dermatol. 2007 Jan;127(1):65-74.
Reference 45 FDA Approved Drug Products from FDA Official Website. 2004. Application Number: (ANDA) 125085.
Cite NPCDR
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Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China