angiogenesis,tyrosine

Cabozantinib (XL184) is a multi-targeted tyrosine kinase receptor inhibitor that inhibits VEGFR2, c-Met, Kit, Axl, and Flt3 (IC50=0.035/1.3/4.6/7/11.3 nM). Cabozantinib exhibits both antitumor and antiangiogenic activity.

Pazopanib (GW786034), a small molecule inhibitor, inhibits multiple protein tyrosine kinases with potential antineoplastic activity. Pazopanib selectively inhibits VEGFR-1, -2 and -3, c-kit and PDGF-R, which may result in inhibition of angiogenesis in tumors in which these receptors are upregulated.

TIE-2/VEGFR-2 kinase-IN-5 is a potent TIE-2 and VEGFR-2 tyrosine kinase receptor inhibitor with anti-angiogenic activity and is commonly used in biomedical research related to angiogenesis.

Cabozantinib hydrochloride (XL184) is a potent pan-tyrosine kinases inhibitor that inhibits VEGFR2, c-Met, Kit, Axl, and Flt4 (IC50s: 0.035, 1.3, 4.6, 7 and 6 nM).

Roblitinib (FGF-401) is an inhibitor of human fibroblast growth factor receptor 4 (FGFR4), with potential antineoplastic activity. Upon administration, Roblitinib binds to and inhibits the activity of FGFR4, which leads to an inhibition of tumor cell proliferation in FGFR4-overexpressing cells. Roblitinib is a receptor tyrosine kinase upregulated in certain tumor cells and involved in tumor cell proliferation, differentiation, angiogenesis, and survival.

Anlotinib is an orally available inhibitor of multiple tyrosine kinases, including human VEGFR1, VEGFR2, VEGFR3, PDGFRβ, and c-Kit with IC50 values of 26.9, 0.2, 0.7, 115, and 14.8 nM, respectively. It demonstrates selectivity for these targets over others like c-Met, c-Src, HER2, and EGFR, which have IC50 values of >2,000 nM. Additionally, anlotinib effectively inhibits FGFR1 with an IC50 of 11.7 nM. Its anti-tumor activity has been confirmed in various cancer cell lines, including colorectal, renal, lung, breast, leukemia, melanoma, and glioblastoma, with IC50s ranging from 3-12.5 μM. Anlotinib also inhibits VEGF-induced endothelial cell migration (IC50= 0.1 nM) and FBS-induced tube formation, contributing to its anti-angiogenic effects. In vivo, it showed a significant reduction in tumor volume and angiogenesis in a SW620 xenograft mouse model at a dose of 3 mg/kg per day, highlighting its potential for cancer therapy.

VE-PTP-IN-1 (compound 2) is a selective inhibitor of the vascular endothelial protein tyrosine phosphatase (VE-PTP), possessing weakly acidic properties. It is associated with the regulation of vascular homeostasis and angiogenesis.

MGCD-265 analog (Glesatinib) is an orally bioavailable multitargeted tyrosine kinase inhibitor with potential antineoplastic activity with IC50 of 29 nM and 10 nM for c-Met and VEGFR2, respectively.

TIE-2/VEGFR-2 kinase-IN-4, a benzimidazole derivative, serves as a potent inhibitor of the tyrosine kinase receptors TIE-2 and VEGFR-2, exhibiting inhibitory concentration (IC50) values of 5.2 nM and 5.1 nM, respectively. This compound is utilized in angiogenesis research [1].

Glutathione glycylethyl ester is a hydrophilic derivative of the protein tyrosine phosphatase inhibitor phenylarsine oxide (PAO). It inhibits angiogenesis and tumour growth.

Glutathione palmitamide is a hydrophilic derivative of the protein tyrosine phosphatase inhibitor phenylarsine oxide (PAO). It inhibits angiogenesis and tumour growth.

DW532 is one of simplified analogues of hematoxylin that has shown broad-spectrum inhibition on tyrosine kinases and in vitro anti-cancer activities. DW532 inhibited EGFR and VEGFR2 in vitro kinase activity (the IC50 values were 4.9 and 5.5 μmol/L, respectively), and suppressed their downstream signaling. DW532 dose-dependently inhibited tubulin polymerization via direct binding to tubulin, thus disrupting the mitotic spindle assembly and leading to abnormal cell division. In a panel of human cancer cells, DW532 (1 and 10 μmol/L) induced G2/M phase arrest and cell apoptosis, which subsequently resulted in cytotoxicity. Knockdown of BubR1 or Mps1, the two core proteins of the spindle assembly checkpoint dramatically decreased DW532-induced cell cycle arrest in MDA-MB-468 cells. Moreover, treatment with DW532 potently and dose-dependently suppressed angiogenesis in vitro and in vivo. ( Acta Pharmacol Sin. 2014 Jul;35(7):916-28.)

Su1498 (Tyrphostin SU 1498) is a selective inhibitor of the receptor tyrosine kinase VEGF receptor 2 (VEGFR2, aka FLK1; IC50 = 700 nM), having negligible activity at several other serine/threonine and tyrosine kinases.1, 2 It effectively blocks signaling through VEGFR2 both in vitro and in vivo.1, 3 SU 1498 is used to study the role of VEGFR2 signaling in diverse processes, including angiogenesis, tumor growth, neural progenitor cell survival, and neuroregeneration.

Tyrphostin AG1433 (AG1433) is an inhibitor of tyrosine kinases and also a dual inhibitor of PDGFRβ(IC50s = 5.0 μM) and VEGFR-2 (Flk-1/KDR)(IC50s = 9.3 μM).

PD-161570 is a potent and ATP-competitive human FGF-1 receptor inhibitor with an IC50 of 39.9 nM and a Ki of 42 nM. PD-161570 also inhibits the PDGFR, EGFR and c-Src tyrosine kinases with IC50 values of 310 nM, 240 nM, and 44 nM, respectively.

Brivanib Alaninate (BMS-582664) is the alaninate salt of a vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor with potential antineoplastic activity. Brivanib strongly binds to and inhibits VEGFR2, a tyrosine kinase receptor expressed almost exclusively on vascular endothelial cells; inhibition of VEGFR2 may result in inhibition of tumor angiogenesis, inhibition of tumor cell growth, and tumor regression.

Glutathione maleimide is a hydrophilic derivative of the protein tyrosine phosphatase inhibitor phenylarsine oxide (PAO). It inhibits angiogenesis and tumour growth.

PKC412(Midostaurin (PKC412); CGP41231; CGP41251) is a broad spectrum protein kinase inhibitor. Midostaurin inhibits protein kinase C alpha (PKCalpha), vascular endothelial growth factor receptor 2 (VEGFR2), c-kit, platelet-derived growth factor receptor (PDGFR) and FMS-like tyrosine kinase 3 (FLT3) tyrosine kinases, which may result in disruption of the cell cycle, inhibition of proliferation, apoptosis, and inhibition of angiogenesis in susceptible tumors.

Potent EGFR-kinase inhibitor (IC50 = 0.7 nM). Displays >3000-fold selectivity against a panel of serine/threonine kinases. Reduces metastasis and angiogenesis in a mouse model of pancreatic cancer. Antihypertensive and orally bioavailable. Bruns et al (2000) Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma. Cancer Res. 60 2926 PMID:10850439 |Ulu et al (2013) Epidermal growth factor receptor inhibitor PKI-166 governs cardiovascular protection without beneficial effects on the kidney in hypertensive 5/6 nephrectomized rats. J.Pharmacol.Exp.Ther. 345 393 PMID:23528611 |Kaspersen et al (2012) Activity of 6-aryl-pyrrolo[2,3-d]pyrimidine-4-amines to Tetrahymena. Bioorg.Chem. 44 35 PMID:22832269

Brivanib Alaninate-d4 is a deuterated compound of Brivanib Alaninate. Brivanib Alaninate has a CAS number of 649735-63-7. Brivanib Alaninate is the alaninate salt of a vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor with potential antineoplastic activity. Brivanib strongly binds to and inhibits VEGFR2, a tyrosine kinase receptor expressed almost exclusively on vascular endothelial cells; inhibition of VEGFR2 may result in inhibition of tumor angiogenesis, inhibition of tumor cell growth, and tumor regression.

TIE-2/VEGFR-2 kinase-IN-3, a benzimidazole derivative, serves as a potent inhibitor of the tyrosine kinase receptors TIE-2 and VEGFR-2, exhibiting IC50 values of 6.9 nM and 3.5 nM, respectively. This compound is useful for angiogenesis research [1].

Protein tyrosine phosphatases (PTPs) remove phosphate from tyrosine residues of cellular proteins. Reversible phosphorylation catalyzed by the coordinated actions of protein tyrosine kinases and phosphatases is key to the regulation of the signaling events that control cell growth and proliferation, differentiation, and survival or apoptosis, as well as adhesion and motility. RK-682, a bioactive compound originally isolated from the fermentation of Streptomyces sp. 88-682, is an inhibitor of the PTPs. It inhibits the phosphorylation of CD45 and VHR with IC50 values of 54 and 2 μM, respectively, and arrests cell cycle progress at the G1/S transition. It is also reported to inhibit heparanase (IC50 = 17 μM), an endo-β-D-glucuronidase involved in tumor cell invasion and angiogenesis. RK-682 (calcium salt) is a less soluble version of the free acid.

Cediranib is a potent and selective inhibitor of VEGF with antineoplastic activities. It inhibits all three vascular endothelial growth factor receptor (VEGF-1,-2,-3) tyrosine kinases, thereby blocking VEGF-signaling, angiogenesis, and tumor cell growth.

Vascular endothelial growth factor receptor 2 (VEGFR2, also known as KDR and FLK1) is a receptor tyrosine kinase that regulates angiogenesis, vascular development, and embryonic hematopoiesis in response to VEGF isoforms A, C, and D. VEGFR2 kinase inhibitor II is a reversible, cell-permeable inhibitor of VEGFR2's kinase activity (IC50 = 70 nM). It less potently inhibits the platelet-derived growth factor receptor β (PDGFRβ; IC50 = 920 nM) and related receptor and non-receptor tyrosine kinases. VEGFR2 kinase inhibitor II blocks the growth of human umbilical vein endothelial cells stimulated with either VEGF or PDGF (IC50s = 110 nM and 2 μM, respectively).

Golvatinib (E-7050) is an orally bioavailable dual kinase inhibitor of c-Met (hepatocyte growth factor receptor) and VEGFR-2 (vascular endothelial growth factor receptor-2) tyrosine kinases with potential antineoplastic activity. c-Met/VEGFR kinase inhibitor E7050 binds to and inhibits the activities of both c-Met and VEGFR-2, which may inhibit tumor cell growth and survival of tumor cells that overexpress these receptor tyrosine kinases. c-Met and VEGFR-2 are upregulated in a variety of tumor cell types and play important roles in tumor cell growth, migration and angiogenesis.

AG1433 is a tyrosine kinases inhibitor that acts as a direct and selective inhibitor of photosynthetic PEP carboxylase and an inhibitor of PDGFR-β, Flk-1, and angiogenesis.

Glutathione sulfinanilide is a hydrophilic derivative of the protein tyrosine phosphatase inhibitor phenylarsine oxide (PAO). It inhibits angiogenesis and tumour growth.

SKLB610, a novel multi-targeted inhibitor, inhibits angiogenesis-related tyrosine kinase VEGFR2, FGFR2, and PDGFR at a rate of 97%, 65%, and 55%, respectively, at the concentration of 10 μM in biochemical kinase assays.

Motesanib (AMG 706) is an orally bioavailable receptor tyrosine kinase inhibitor with potential antineoplastic activity. AMG 706 selectively targets and inhibits vascular endothelial growth factor (VEGFR), platelet-derived growth factor (PDGFR), Kit, and Ret receptors, thereby inhibiting angiogenesis and cellular proliferation.

Glutathione sulfonate is a hydrophilic derivative of the protein tyrosine phosphatase inhibitor phenylarsine oxide (PAO). It inhibits angiogenesis and tumour growth.

Glutathione sodium is a hydrophilic derivative of the protein tyrosine phosphatase inhibitor phenylarsine oxide (PAO). It inhibits angiogenesis and tumour growth.

Vorolanib (X-82) is an orally active VEGFR/PDGFR dual inhibitor.

Glutathione diethyl ester is a hydrophilic derivative of the protein tyrosine phosphatase inhibitor phenylarsine oxide (PAO). It inhibits angiogenesis and tumour growth.

PF-00337210 is an orally available ATP-competitive inhibitor of the vascular endothelial growth factor receptor type 2 (VEGFR2), with potential anti-angiogenesis and antineoplastic activities. Upon administration, the VEGFR2 tyrosine kinase inhibitor PF-00337210 selectively binds to VEGFR2 and prevents its phosphorylation which may result in an inhibition of migration, proliferation and survival of endothelial cells, microvessel formation, the inhibition of tumor cell proliferation, and may eventually cause tumor cell death. VEGFR2, a receptor tyrosine kinase, is frequently overexpressed by a variety of tumor types.

SIM010603 is a structurally novel, oral, multi-targeted receptor tyrosine kinase inhibitor. SIM010603 inhibited stem cell factor receptor (Kit), vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor receptor-β (PDGFR-β), glial cell line-derived neurotrophic factor receptor (Rearranged during Transfection; RET), and Fms-like tyrosine kinase-3 (FLT3) with IC(50) values between 5.0 and 68.1 nmol/l. SIM010603 inhibited the phosphorylation of PDGFR-β and VEGFR-2. Moreover, SIM010603 inhibited endothelial cell proliferation, endothelial cells chemotaxis, and corneal angiogenesis.