flk1

Semaxinib (SU5416) is a potent and selective VEGFR2 inhibitor (IC50: 1.23 μM), exhibiting a 20-fold greater selectivity for VEGFR2 over PDGFRβ, with no activity against InsR, EGFR, and FGFR. Semaxinib reversibly inhibits ATP binding to the tyrosine kinase domain of VEGFR2, potentially inhibiting VEGF-stimulated endothelial cell migration and proliferation, thereby reducing tumor microvasculature.

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.

Brivanib (BMS-540215) is an ATP-competitive inhibitor targeting VEGFR2 with an IC50 of 25 nM, exhibiting moderate potency against VEGFR-1 and FGFR-1, and over 240-fold selectivity against PDGFR-β. Phase 3.

Orantinib (NSC 702827) , a excellent effective against PDGFR autophosphorylation with Ki of 8 nM, also highly inhibits Flk-1 and FGFR1 trans-phosphorylation. It shows little effect against IGF-1R, Met, Src, Lck, Zap70, Abl and CDK2 and does not suppresses EGFR.

SU5205 is a VEGFR2 inhibitor.

SU5214 is a modulator of tyrosine kinase signal transduction.

Axitinib (AG-013736) is a multi-targeted tyrosine kinase inhibitor that inhibits VEGFR1, VEGFR2, VEGFR3, and PDGFRβ (IC50=4/20/0.4/2 nM). Axitinib has antitumor activity and is used in the treatment of renal cell carcinoma.

Sorafenib tosylate (Bay 43-9006) is a potent multikinase inhibitor (IC50s: 6 20 22 nM for Raf-1 VEGFR-3 B-Raf).

Cediranib (AZD2171) (AZD2171) is a highly potent (IC50 < 1 nmol L) ATP-competitive inhibitor of recombinant KDR tyrosine kinase in vitro, also inhibits Flt1 4 (IC50: 5 nM ≤3 nM), similar activity against PDGFRβ and c-Kit, selective more for VEGFR than PDGFR-α (36-fold), CSF-1R (110-fold), and Flt3 (1000-fold) in HUVEC cells.

Toceranib Phosphate (SU11654 phosphate), is a selective inhibitor of the tyrosine kinase activity of several members of the split kinase RTK family, including Flk-1 KDR, PDGFR

(Z)-Semaxinib (SU5416) is a potent and selective VEGFR(Flk-1 KDR) inhibitor (IC50: 1.23 μM), 20-fold more selective for VEGFR over PDGFRβ, no inhibition for FGFR, InsR, and EGFR. (Z)-Semaxinib is a quinolone derivative with potential antineoplastic activity.

PHA-665752 is an effective, specific and ATP-competitive c-Met inhibitor (IC50: 9 nM), >50-fold selectivity for c-Met than STKs or RTKs.

BMS-605541 is a potent and selective inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) kinase activity(Ki=49 nM).

Toceranib (PHA 291639E) phosphate is an orally active inhibitor of tyrosine kinase (RTK) receptor, and it potently inhibits PDGFR, VEGFR, and Kit(with Kis of 5 and 6 nM for PDGFRβ and Flk-1 KDR, respectively), has antitumor and antiangiogenic activity.

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).

Rigosertib (ON-01910) is a selective, non-ATP-competitive PLK1 inhibitor (IC50: 9 nM) and multi-kinase inhibitor. As a selective anti-cancer agent, Rigosertib induces apoptosis by inhibiting the PI3 kinase/Akt pathway, promotes histone H2AX phosphorylation, and induces G2/M arrest in the cell cycle.

AEE788 (NVP-AEE 788) has been used in trials studying the treatment of Cancer, Glioblastoma Multiforme, and Brain and Central Nervous System Tumors.

Motesanib Diphosphate (AMG 706) is the orally bioavailable diphosphate salt of a multiple-receptor tyrosine kinase inhibitor with potential antineoplastic activity.

VEGFR inhibitor

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.

Linifanib (AL-39324) (ABT-869) is a novel, potent ATP-competitive VEGFR/PDGFR inhibitor for KDR (IC50: 4 nM), CSF-1R (IC50: 3 nM), Flt-1/3 (IC50: 3/4 nM) and PDGFRβ (IC50: 66 nM). Linifanib may exhibit potent antiproliferative and apoptotic effects on tumor cells whose proliferation is dependent on mutant kinases, such as FMS-related tyrosine kinase receptor-3 (FLT3).

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.

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.

Chiauranib is a multi-target inhibitor against tumor angiogenesis and exhibits potent anticancer effects. Chiauranib potently inhibits the angiogenesis-related kinases (VEGFR1, VEGFR2, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B, and chronic inflammation-related kinase CSF1R, with IC50 values ranging from 1-9 nM.