angiogenesis inhibitor

Angiogenesis Inhibitor 4 is a potent agent for inhibiting angiogenesis, with potential applications in cancer research [1].

Angiogenesis inhibitor BT2 is a novel inhibitor of angiogenesis and vascular permeability, inhibiting ERK phosphorylation and the expression of FosB/ΔFosB, VCAM-1, and many genes involved in proliferation, migration, angiogenesis, and inflammation, interacting with MEK1, suppressing retinal CD31, pERK, VCAM-1, and VEGF-A165 expression.

Angiogenesis Inhibitor 3 (Compound 8) is a potent substance that effectively inhibits the growth of HUVEC and HCT-15 cells, demonstrating IC50 values of 1.00 and 0.71 μM, respectively. It not only induces apoptosis in these cells but also exhibits significant anticancer activity by suppressing cancer cell invasion. Furthermore, this compound successfully inhibits angiogenesis in zebrafish embryos [1].

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.

Nintedanib (Intedanib) is a triple vascular kinase inhibitor that inhibits VEGFR1, VEGFR2, and VEGFR3 (IC50=34/13/13 nM), FGFR1, FGFR2, and FGFR3 (IC50=69/37/108 nM), PDGFRα, and PDGFRβ (IC50=59/65 nM). Nintedanib has antitumor activity and inhibits tumor growth by inhibiting angiogenesis.

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.

(Rac)-Arnebin 1 (beta, beta-dimethylacrylshikonin) has anti-tumor, anti-inflammatory, anti-immune deficiency and protecting liver.

Formononetin (Flavosil) is an O-methylated isoflavone and a phytoestrogen from the root of Astragalus membranaceus.

Tranilast (SB 252218), an antiallergic drug, suppresses lipid mediator and cytokine release from inflammatory cells, therefore utilized in the treatment of allergic disorders.

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.

Kisspeptin-10, human TFA is a potent vasoconstrictor and angiogenesis inhibitor. Kisspeptin-10, human TFA acts as a tumor metastasis suppressor via its receptor GPR54. Kisspeptin-10-GPR54 system plays an important role in embryonic kidney development. Kisspeptin-10/GPR54 signaling induces osteoblast differentiation via NFATc4-mediated BMP2 expression

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).

MMPP is a novel VEGFR2 inhibitor with anti-inflammatory and potential anticancer activity, inhibits STAT3, inhibits angiogenesis via VEGFR2/AKT/ERK/NF-kappaB pathway, and can be used to alleviate myocardial injury.

R1498 is an inhibitor of cyclin-dependent kinase 2. It also acts by targeting angiogenesis and mitosis pathways. It is well-tolerated and orally active for hepatocellular carcinoma and gastric cancer treatment.

Batimastat (BB94) (BB-94) is an effective, broad-spectrum matrix metalloprotease (MMP) inhibitor. Batimastat induces extracellular matrix degradation and inhibits angiogenesis, tumor growth and invasion, and metastasis.

Hexylresorcinol (4-Hexylresorcinol) is a substituted dihydroxybenzene used topically as an antiseptic for the treatment of minor skin infections.

OSI-930, an orally active inhibitor of c-Kit and the vascular endothelial growth factor receptor-2 (VEGFR-2), targets cancer cell proliferation and blood vessel growth (angiogenesis) in tumors.

TNP-470 is a methionine aminopeptidase-2 inhibitor. TNP-470 is also an angiogenesis inhibitor.

Royal Jelly acid (Queen Bee Acid) is an inhibitor of VEGF-induced angiogenesis, cell migration and proliferation.

Rac-Belinostat (PX-105684) is a novel hydroxamic acid-type histone deacetylase (HDAC) inhibitor with antineoplastic activity. Belinostat targets HDAC enzymes, thereby inhibiting tumor cell proliferation, inducing apoptosis, promoting cellular differentiation, and inhibiting angiogenesis. This agent may sensitize drug-resistant tumor cells to other antineoplastic agents, possibly through a mechanism involving the down-regulation of thymidylate synthase.

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.

Ibuprofen (Advil) is a propionic acid derivate and nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic effects. Ibuprofen inhibits the activity of cyclo-oxygenase I and II, resulting in a decreased formation of precursors of prostaglandins and thromboxanes.

GSK126 (GSK2816126A) is a excellently specific EZH2 methyltransferase inhibitor ( IC50=9.9 nM).

EHop-016 is a specific Rac GTPase inhibitor with IC50 of 1.1 μM for Rac1 in MDA-MB-231 and MDA-MB-435 cells, equally effective inhibition for Rac3.

SC144 is an orally active small-molecule gp130 inhibitor.

DB21, Galectin-1 Antagonist, is a peptidomimetic conjugated with dibenzofuran, serving as an allosteric inhibitor of galectin-1 (GAL1) interactions with glycans on cell surfaces. This compound enhances the inhibition of angiogenesis and tumor growth in melanoma, lung adenocarcinoma, and ovarian cancer models [1].

PNU-145156E (FCE26644) a novel angiogenesis inhibitor, has been shown to block circulating angiogenesis promoting growth factor in animal studies and has shown anti-tumor effects in solid tumors in mice.

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.

Phosphatidylserine is a naturally occurring phospholipid that comprises 2-10% of total phospholipids in mammals and is enriched in the central nervous system, particularly the retina. It is anionic and found mainly on the inner leaflet of the cell membrane. It is biosynthesized from phosphatidylcholine or phosphatidylethanolamine by phosphatidyl synthase 1 (PSS1) or PSS2, respectively, in the endoplasmic reticulum and can be reversibly converted back by the same enzymes. It can also be irreversibly converted to phosphatidylethanolamine by phosphatidylserine decarboxylase in the mitochondria. Phosphatidylserine binds to T cell immunoglobulin mucin type 1 (TIM-1) and TIM-4 receptors as well as brain-specific angiogenesis inhibitor 1 (BAI1), leading to anti-inflammatory and anti-atherosclerotic effects. It is also a cofactor involved in the activation of various signaling pathways through activation of protein kinase C, neutral sphingomyelinase, and c-Raf-1 protein kinase among others. Phosphatidylserine is externalized during apoptosis by scramblases in the plasma membrane as a signal for phagocytes to engulf the cell. Phosphatidylserines (bovine) is a mixture of bovine phosphatidylserines containing fatty acids with variable chain lengths at the sn-1 and sn-2 positions.

RWJ-56110 dihydrochloride is a potent, selective, peptide-mimetic inhibitor of PAR-1 activation and internalization (binding IC50=0.44 uM) and shows no effect on PAR-2, PAR-3, or PAR-4. RWJ-56110 dihydrochloride inhibits the aggregation of human platelets induced by both SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM), quite selective relative to U46619 . RWJ-56110 dihydrochloride blocks angiogenesis and blocks the formation of new vessels in vivo. RWJ-56110 dihydrochloride induces cell apoptosis[1][2]. Proteinase-activated receptors (PARs) are a family of G protein-coupled receptors activated by the proteolytic cleavage of their N-terminal extracellular domain, exposing a new amino terminal sequence that functions as a tethered ligand to activate the receptors.RWJ56110 inhibits the aggregation of human platelets induced by both SFLLRN-NH2 (IC50=0.16 μM) and thrombin (IC50=0.34 μM) while being quite selective relative to collagen and the thromboxane mimetic U46619 [1].RWJ-56110 dihydrochloride is fully inhibits thrombin-induced RASMC proliferation with an IC50 value of 3.5 μM. RWJ-56110 dihydrochloride shows blockade of thrombin's action with RASMC calcium mobilization (IC50=0.12 μM), as well as with HMVEC (IC50=0.13 μM) and HASMC calcium mobilization (IC50=0.17 μM)[1].RWJ56110 (0.1-10 μM; 24-96 hours) inhibits endothelial cell growth dose-dependently, with half-maximal inhibitory concentration of RWJ56110 is approximately 10 μM[2].RWJ56110 (0.1-10 μM; 6 hours) inhibits DNA synthesis of endothelial cells in a thymidine incorporation assays. Endothelial cells are in fast-growing state (50-60% confluence), RWJ56110 inhibits cell DNA synthesis in a dose-dependent manner, but when cells that are in the quiescent state (100% confluent), the inhibitory effect of PAR-1 antagonists is much less pronounced[2].RWJ56110 (0.1-10 μM; pretreatment for 15 min) inhibits thrombin-induced Erk1/2 activation in a concentration-dependent manner. However, when endothelial cells are stimulated by FBS (final concentration 4%), it reduces partially the activated levels of Erk1/2[2].RWJ56110 (30 μM; 24 hours) has an inhibitory effect on endothelial cell cycle progression. It reduces the percentage of cells in the S phase, while alterations in the percentages of G1 and G2/M cells are less pronounced[2]. Western Blot Analysis[2] Cell Line: Endothelial cells [1]. Andrade-Gordon, et al.Design, synthesis, and biological characterization of a peptide-mimetic antagonist for a tethered-ligand receptor. oc Natl Acad Sci U S A. 1999 Oct 26;96(22):12257-62. [2]. Panagiota Zania, et al. Blockade of angiogenesis by small molecule antagonists to protease-activated receptor-1: association with endothelial cell growth suppression and induction of apoptosis. J Pharmacol Exp Ther. 2006 Jul;318(1):246-54.

Phosphatidylserine is a naturally occurring phospholipid that comprises 2-10% of total phospholipids in mammals and is enriched in the central nervous system, particularly the retina. It is anionic and found mainly on the inner leaflet of the cell membrane. It is biosynthesized from phosphatidylcholine or phosphatidylethanolamine by phosphatidyl synthase 1 (PSS1) or PSS2, respectively, in the endoplasmic reticulum (ER) and can be reversibly converted back by the same enzymes. It can also be irreversibly converted to phosphatidylethanolamine by phosphatidylserine decarboxylase in the mitochondria. Phosphatidylserine binds to T cell immunoglobulin mucin type 1 (TIM-1) and TIM-4 receptors as well as brain-specific angiogenesis inhibitor 1 (BAI1), leading to anti-inflammatory and anti-atherosclerotic effects. It is also a cofactor involved in the activation of various signaling pathways through activation of protein kinase C, neutral sphingomyelinase, and c-Raf-1 protein kinase among others. Phosphatidylserine is externalized during apoptosis by scramblases in the plasma membrane as a signal for phagocytes to engulf the cell. Phosphatidylserines (soy) is a mixture of soy phosphatidylserines containing fatty acids with variable chain lengths at the sn-1 and sn-2 positions.

AT-533 is a potent inhibitor of Hsp90 and HSV. AT-533 blocks the HIF-1α/VEGF/VEGFR-2 signaling pathway, leading to suppress tumor growth and angiogenesis. AT-533 also inhibits the activation of the downstream pathways, including Erk1/2, FAK, Akt/mTOR/p70S6K,. AT-533 inhibits the cell migration, invasion, and the tube formation of human umbilical vein endothelial cells (HUVECs).

Gersizangitide acetate is an inhibitor of angiogenesis.

Kisspeptin-10, human is an effective vasoconstrictor and inhibitor of 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.

Highly potent integrin α1β1 inhibitor (IC50 = 0.8 nM for α1β1 binding to type IV collagen). Selective for α1β1 over α2β1, αIIbβ3, αvβ3, α4β1, α5β6, α9β1 and α4β7. Inhibits FGF2-stimulated angiogenesis in the chicken chorioallantoic model. Displays antitum

HA 155 (Autotaxin Inhibitor IV) is a boronic acid-based compound, inhibiting ATX with IC50 of 5.7 nM by selectively binding to its catalytic threonine.

Obtustatin triacetate, a 41-residue non-RGD disintegrin isolated from the venom of Vipera lebetina obtusa, serves as a potent and selective inhibitor of the integrin α1β1's adhesion to type IV collagen. This compound holds significance in cancer research due to its ability to inhibit angiogenesis [1].

Sotiburafusp alfa is a humanized bispecific fusion protein comprising a VEGFR-1 extracellular domain fragment (129-228, 1-100 in the current sequence) connected through a 101 GGSGGSGGSGGSGGS 115 peptide linker to the N-terminus (116-564) of a humanized IgG1-kappa anti-human PD-L1 heavy chain with L352>A and L353>A mutations. Additionally, sotiburafusp alfa functions as an angiogenesis inhibitor [1].

MPT0B390 is an inhibitor of HDAC and a TIMP3 inducer inhibiting tumor growth, metastasis, and angiogenesis.

JK-P3 is a pyrazole-based inhibitor of VEGFR-2 (IC50: 7.8 μM). JK-P3 inhibits FGFR 1/3 kinase activity in vitro, but has no effect on FGFR signaling in cell-based assays. The compound blocks wound healing and tube formation in HUVEC without effecting endo

Hyperforin acts as an angiogenesis inhibitor, it as a possible antidepressant component of hypericum extracts.

Beloranib is a fumagillin anticancer drug. Beloranib belongs to an angiogenesis inhibitor.

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].

Silymarin (Silybin B) (Silybin B) is a polyphenolic flavonoid that extracts from the milk thistle or seeds of Silybum marianum. It is used in the prevention and treatment of liver diseases.

Rebimastat is a sulfhydryl-based second-generation matrix metalloproteinase (MMP) inhibitor with potential antineoplastic activity. Rebimastat selectively inhibits several MMPs (MMP 1, 2, 8, 9, and 14), thereby inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis.

MYLS22 is a first-in-class and selective inhibitor of optic atrophy 1 (OPA1) . MYLS22 can target endothelial OPA1 to curtail tumor growth and inhibits angiogenesis by impinging on NFkB activity and on angiogenic gene expression. It with anti-angiogenesis and anti-cancer activity.

Ganglioside GM3 is a monosialoganglioside that demonstrates antiproliferative and proapoptotic effects in tumor cells by modulating cell adhesion, proliferation, and differentiation. It suppresses angiogenesis and reduces proliferation and migration of human umbilical vein endothelial cells (HUVECs) when used at a concentration of 20 μM via inhibition of VEGFR2 and Akt phosphorylation. Ganglioside GM3 induces dissociation of the insulin receptor-caveolin-1 complex from lipid microdomains, functioning as an inhibitor of insulin signaling and contributing to insulin resistance in adipocytes. Ganglioside GM3 mixture contains ganglioside GM3 molecular species with C18:1 and C20:1 fatty acyl chains.

LY5 is an inhibitor of STAT3 that acts by inhibiting cell viability, cell migration, and angiogenesis in medulloblastoma cells.

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.