Product Categories

VEGFR Vascular Endothelial Growth Factor Receptor

VEGFR Inhibitors (44)

water-soluble

Cat.No. Product Name Information Product Citations Customer Reviews
S1119 XL-184 free base (Cabozantinib) XL184 (Cabozantinib) is a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM, respectively.
S1010 BIBF1120 (Vargatef) BIBF1120 (Vargatef) is a potent inhibitor of VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM, respectively.
S1046 Vandetanib (Zactima) Vandetanib (Zactima, ZD6474) is a potent inhibitor of VEGFR2 with IC50 of 40 nM.
S1035 Pazopanib HCl Pazopanib Hydrochloride (GW786034, Votrient, Armala) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM, respectively.
S1005 Axitinib Axitinib (AG-013736) is a multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ and c-Kit with IC50 of 0.1 nM, 0.2 nM, 0.1-0.3 nM, 1.6 nM and 1.7 nM, respectively.
S7082 TAK-593 TAK-593 is a novel dual VEGFR/PDGFR inhibitor.
S4001 Cabozantinib malate Cabozantinib malate is the malate of Cabozantinib, a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM, respectively.
S2018 ENMD-2076 L-(+)-Tartaric acid ENMD-2076 L-(+)-Tartaric acid is the tartaric acid of ENMD-2076, a selective inhibitor of Aurora A and Aurora B with IC50 of 14 nM and 350 nM and also inhibits Flt3, Flt4 and VEGFR2 with IC50 of 1.86 nM, 15.9 nM and 58.2 nM, respectively.
S1040 Sorafenib (Nexavar) Sorafenib Tosylate (Bay 43-9006, Nexavar) is a multikinase inhibitor of Raf-1, B-Raf and VEGFR-2 with IC50 of 6 nM, 22 nM and 90 nM, respectively.
S1042 Sunitinib Malate (Sutent) Sunitinib Malate (Sutent, SU11248) is a multi-targeted RTK inhibitor targeting VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM, and also inhibits c-Kit.
Cat.No. Product Name Information Product Citations Customer Reviews
S1490 Ponatinib (AP24534) AP24534 is a novel, potent multi-target inhibitor of Abl, PDGFRα, VEGFR2, FGFR1 and Src with IC50 of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM and 5.4 nM, respectively.
S1178 Regorafenib (BAY 73-4506) Regorafenib (BAY 73-4506, Fluoro-Sorafenib) is a multi-target inhibitor for VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit, RET and Raf-1 with IC50 of 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM, respectively.
S1264 PD173074 PD173074 is a potent FGFR1 inhibitor with IC50 of ~25 nM and also inhibits VEGFR2 with IC50 of 100-200 nM.
S1111 Foretinib (GSK1363089, XL880) XL880 (GSK1363089, EXEL-2880) is an ATP-competitive inhibitor of MET and KDR with IC50 of 0.4 nM and 0.9 nM, respectively.
S1018 Dovitinib (TKI-258) Dovitinib (TKI258, CHIR258) is a novel multi-target inhibitor for Flt3, c-Kit, FGFR1/3, VEGFR1/2/3, PDGFRα/β with IC50 of 1 nM, 2 nM, 8 nM/9 nM and 10 nM/13 nM/8 nM, 210 nM/27 nM respectively.
S1017 Cediranib (AZD2171) Cediranib (AZD2171) is a highly potent VEGFR2 inhibitor with IC50 of 0.5 nM, also inhibits Flt1/4 with IC50 of 5 nM/≤3 nM.
S2161 RAF265 (CHIR-265) RAF265 (CHIR-265) is a selective and potent inhibitor of B-Raf and VEGFR2 with IC50 of 3-60 nM and EC50 of 30 nM, respectively.
S1207 Tivozanib (AV-951) AV-951 (Tivozanib, KRN-951) is a potent and selective VEGFR inhibitor for VEGFR1/2/3 with IC50 of 0.21 nM/0.16 nM/0.24 nM and also inhibits PDGFR and c-Kit with IC50 of 1.72 nM and 1.63 nM, respectively.
S1470 TSU-68 (SU6668) TSU-68 (SU6668, Orantinib) is a potent inhibitor of Flk-1/KDR, FGFR1 and PDGFRβ with Ki of 2.1 μM, 1.2 μM, and 8 nM, respectively.
S1084 Brivanib (BMS-540215) Brivanib is an ATP-competitive inhibitor against human VEGFR2 and FGFR with IC50 of 25 nM and 148 nM, respectively.
Cat.No. Product Name Information Product Citations Customer Reviews
S1164 E7080 (Lenvatinib) E7080 (Lenvatinib) is a multi-target inhibitor of VEGFR2 and VEGFR3 with IC50 of 4 nM and 5.2 nM, respectively.
S1003 Linifanib (ABT-869) Linifanib (ABT-869) is a novel, potent ATP-competitive RTK inhibitor for KDR, CSF-1R, Flt-1, Flt-3 and PDGFRβ with IC50 of 4 nM, 3 nM, 3 nM, 3 nM, and 66 nM respectively.
S1101 Vatalanib 2HCl (PTK787) Vatalanib (PTK787) is an inhibitor of VEGFR2/KDR, Flt-1 and c-Kit with IC50 of 37 nM, 77 nM and 730 nM, respectively.
S1361 MGCD-265 MGCD-265 is a potent, multi-target and ATP-competitive inhibitor of c-Met, VEGFR1, VEGFR2, VEGFR3, Ron, and Tie2 with IC50 of 1 nM, 3 nM, 3 nM, 4 nM, 2 nM and 7 nM, respectively.
S2842 SAR131675 SAR131675 is a VEGFR-3 inhibitor with IC50 of 20 nM.
S1032 Motesanib Diphosphate (AMG-706) Motesanib Diphosphate (AMG-706) is a potent ATP-competitive inhibitor of VEGFR1/2/3, PDGFR, c-Kit and Ret with IC50 of 2 nM/3 nM/6 nM, 84 nM, 8 nM and 59 nM, respectively.
S2202 NVP-BHG712 NVP-BHG712 is a specific inhibitor of c-Raf, c-Src and c-Abl with IC50 of 0.395 μM, 1.266 μM and 1.667 μM and also inhibits EphB4 and VEGFR2 with ED50 of 25 nM and 4.2 μM, respectively.
S3012 Pazopanib Pazopanib is a potent and selective multi-targeted receptor tyrosine kinase inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR-α/β, and c-Kit.
S2769 Dovitinib Dilactic acid (TKI258 Dilactic acid) Dovitinib (TKI258, CHIR-258) is a multitargeted tyrosine kinase inhibitor of FLT3 and c-KIT with IC50 of 1 nM and 2 nM, respectively.
S1181 ENMD-2076 ENMD-2076 is a selective inhibitor of Aurora A and Aurora B with IC50 of 14 nM and 350 nM and also inhibits Flt3, Flt4 and VEGFR2 with IC50 of 1.86 nM/15.9 nM and 58.2 nM, respectively.
Cat.No. Product Name Information Product Citations Customer Reviews
S2859 Golvatinib (E7050) E7050 is a dual c-Met and VEGFR-2 inhibitor with IC50 of 14 nM and 16 nM, respectively.
S1171 CYC116 CYC116 is a potent inhibitor of Aurora A/B and VEGFR with Ki of 8.0 nM/9.2 nM and 44 nM, respectively.
S1220 OSI-930 OSI-930 is a potent inhibitor of Kit, KDR, Flt, CSF-1R, c-Raf and Lck with IC50 of 80 nM, 9 nM, 8 nM, 15 nM, 41 nM and 22 nM, respectively.
S1363 Ki8751 Ki8751 is a potent and selective inhibitor of VEGFR2, PDGFRα and c-Kit with IC50 of 0.9 nM, 67 nM and 40 nM, respectively.
S2231 Telatinib (BAY 57-9352) Telatinib (BAY 57-9352) is a potent inhibitor of VEGFR2/3, c-Kit and PDGFRβ with IC50 of 6 nM/4 nM, 1 nM and 15 nM, respectively.
S1138 Brivanib alaninate (BMS-582664) BMS-582664 is an oral VEGFR/FGFR inhibitor for VEGFR2, Flk1, VEGFR1 and FGFR1 with IC50 of 25 nM, 89 nM, 380 nM and 148 nM, respectively.
S1486 AEE788 (NVP-AEE788) AEE788 is a potent inhibitor of EGFR and HER2/ErbB2 with IC50 of 2 nM and 6 nM and also inhibits VEGFR2 and Flt with IC50 of 77 nM and 59 nM, respectively.
S1557 KRN 633 KRN 633 is an ATP-competitive inhibitor of VEGFR1/2/3 with IC50 of 170 nM/160 nM/125 nM and also inhibits PDGFRα/β with IC50 of 965 nM/9850 nM.
S2221 Apatinib (YN968D1) Apatinib (YN968D1) is an orally bioavailable, selective VEGFR2 inhibitor with IC50 of 1 nM.
S2896 ZM 323881 HCl ZM-323881 is a potent and selective inhibitor of VEGFR2 with IC50 < 2 nM.
Cat.No. Product Name Information Product Citations Customer Reviews
S2201 BMS 794833 BMS794833 is a potent ATP competitive inhibitor of Met and VEGFR2 with IC50 of 1.7 nM and 15 nM, respectively.
S2200 Raf265 derivative A derivative of Raf265. But the effects of this derivative is not known.
S2845 Semaxanib (SU5416) Semaxanib (SU5416) is a potent and selective VEGFR (Flk-1/KDR) inhibitor with IC50 of 1.04 μM.
S2897 ZM 306416 ZM-306416 is a VEGFR inhibitor, inhibiting Src, VEGFR1 and Abl with IC50 of 0.33 μM, 0.33 μM and 1.3 μM, respectively.
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All VEGFR Inhibitors

Solid tumors require the growth and dissemination of blood vessels and lymphatic vessels to support the metastatic growth of cancers. Following the recognition of growth factor receptor pathways that regulate angiogenesis, a number of small molecular inhibitors and antibodies have been developed that target the activity of vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR) pathway. This includes oral small-molecule tyrosine kinase inhibitors currently in clinical practice, namely sunitinib and sorafenib. These are commonly used in the treatment algorithm for renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC), two indications that are known to develop resistance to conventional chemotherapeutics.

The VEGFs include five known structurally-related mammalian ligands (VEGFA, VEGFB, VEGFC, VEGFD, and placenta growth factor, PLGF). The VEGFs are disulfide-bonded homodimers, however, VEGFA and PLGF heterodimers are also known to exist. Due to alternative splicing or due to processing, VEGF ligands occur as several different variants. As a result, these variants bind differently to both VEGFRs and to co-receptors resulting in different biological responses including angiogenesis, lymphangiogenesis, permeability, inflammatory cell recruitment and fatty acid uptake. VEGFs are produced by several different cell types and act in a paracrine manner. The VEGFs bind to three structurally related tyrosine kinases (VEGFR1, VEGFR2, and VEGFR3). Modulating the effect of the VEGFRs are a number of co-receptors that lack intrinsic catalytic activity (i.e. heparin sulfate, neurophilins and integrins) and bind to VEGF.[1]

VEGFR1 (also known as Fms-like tyrosine kinase 1, Flt1, in mice) is a single-transmembrane glycoprotein structurally related to VEGFR2 and VEGFR3. VEGFR1 is expressed at high levels in vascular endothelial cells, and along with VEGFR2 binds to VEGFA. VEGFR1 is noted to bind exclusively to VEGFB and PIGF. Expression of VEGFR1 is noted to occur during vessel growth and remodeling activity. Non-endothelial cells that express VEGFR1 includes monocytes and macrophages, human tropholblasts, renal mesangial cells, vascular smooth muscle cells, dendritic cells and various tumor cells. A key regulator of VEGFR1 gene expression is hypoxia.[1]

VEGFR2 (also known as KDR; kinase insert domain receptor, in the human and Flk1; fetal liver kinase-1, in mice) binds VEGFA with a 10-fold lower affinity than VEGFR1.  Other targets of VEGFR2 include proteolytically processed VEGFC and VEGFD. The only known ligand to uniquely bind to VEGFR2 is the open reading frame-encoded VEGFE. VEGFR2 is expressed in most adult vascular endothelial cells as well as circulating endothelial progenitor cells, pancreatic duct cells, retinal progenitor cells, megakaryocytes and hematopoietic cells. VEGFR2 expression is induced in conjunction with active angiogenesis (i.e. the uterus during the reproductive cycle) and in pathological process related to neovascularization (i.e. cancer). VEGFR2, often in combination with VEGFR3, is expressed at significantly upregulated levels in the tumor vascular endothelium in most common human solid tumors. Tumor cells can also express VEGFR2, however, epithelial and mesenchymal tumor cells typically express VEGFR1 rather than VEGFR2. Nevertheless, increased expression of VEGFR2  on tumor cells has been noted for melanoma and hematological malignancies. And, there is evidence supporting a relationship between chronic inflammation and tumor development.[1]

VEGFR3 (also known as Fms-like tyrosine kinase 4, Flt4 in the mouse) is activated by the binding of VEGFC or VEGFD, once these two ligands undergo proteolytic processing (this increases their affinity to VEGFR2 and VEGFR3). In addition, hVEGFD shows similar affinity to both VEGFR2 and VEGFR3, while mVEGFD binds only to VEGFR3. During embryogenesis, VEGFR3 expression occurs in the primary vascular plexus at day E8.5. In late stages of embryogenesis, VEGFR3 is expressed in venous endothelial cells of the cardinal vein, that results in VEGFR3-expressing lymphatics. Postnatally, VEGFR3 plays an important role in lymphatic endothelial cells, but its expression is also observed in endothelial cells engaged in active angiogenesis, such as tumor vessels, in endothelial tip cells of angiogenic sprouts in the developing retina or in chronic inflammatory wounds. The receptor is also found in non-endothelial cells such as osteoblasts, neuronal progenitors and macrophages – all of which may indirectly support angiogenesis. It remains unclear if tumor cells express VEGFR3. Despite this lack of clarity, inhibiting VEGFR3 activity is associated with the arrest of tumor vascularization, resulting in decreased vascular density in several tumor models.[1]

Since the VEGF-VEGFR pathway plays a significant role in angiogenesis, and it is widely known that VEGF is highly expressed in tumor and stromal cells, especially in the inflammatory cells of human tumors, dozens of angiogenesis inhibitors are currently undergoing clinical trials.[2] However, despite the number of compounds that has been identified for targeting the VEGF-VEGFR pathway, there is a high attrition rate. Several challenges in the development of angiogenesis inhibitors relate to their specificity, efficacy, side effects, and resistance to anti-angiogenic tumor therapy. However, the emergence of personalized medicine – based on the use of biomarkers – will likely lead to the identification of patient populations that is likely to define respondent groups.

References

[1] Tugues, S., Koch, S., Gualandi, L., Xiujuan, L., and Claesson-Welsh L. Vascular endothelial growth factors and receptors: Anti-angiogenic therapy in the treatment of cancer. Molecular Aspects of Medicine 2011; 32: 88-111.
[2] Saharinen, P., Eklund, L., Pulkki, K., Bono, P., and Alitalo, K. VEGF and angiopoietin signaling in tumor angiogenesis and metastasis. Trends in Molecular Medicine 2011; 17(7): 347-367.

Tags: VEGFR inhibition | VEGFR cancer | VEGFR2 cancer | VEGFR pathway | VEGFR phosphorylation | VEGFR2 phosphorylation | VEGFR signaling pathway | VEGFR assay | VEGFR inhibitor drug | VEGFR inhibitor review