SU5416 (Semaxanib) is a potent and selective vascular endothelial growth factor (VEGF) receptor protein tyrosine kinase 1/2 inhibitor that also inhibits other tyrosine kinases KIT, MET, FLT3 and RET. SU5416 inhibited cell migration of human vascular endothelial cells expressing both Flt-1 and KDR in response to VEGF and also inhibited the cell migration in response to placenta growth factor (PIGF), a specific ligand for Flt-1. Chemotaxis of monocytes expressing only Flt-1 was also inhibited by SU5416 in a dose-dependent manner. Moreover, SU5416 was found to inhibit tyrosine kinase of Flt-1 in response to PIGF in vitro. SU5416 efficiently inhibited Kit activity in vivo when administered on a twice-weekly schedule.
|Cell lines||C6, Calu 6, A375, A431, and SF767T|
|Preparation method||Tumor Cell Lines and Growth Assays. The EPH4-VEGF cell line is a murine epithelial cell line engineered to overexpress murine VEGF. EPH4-VEGF cells were cultured in DMEM/F-12; C6 cells were cultured in Ham’s F-10 and A375, A431, and LNCAP cells in DMEM. All of these cultures were supplemented with 10% FBS and 2 mM L-glutamine. Calu 6 and SF767T cells were cultured in MEM supplemented with 10% FBS, 2 mM L-glutamine, 1 mM sodium pyruvate, and 0.1 mM MEM nonessential amino acids solution. C6, Calu 6, A375, A431, and SF767T were plated in their respective growth medium at 2 × 103 cells/100 μl/well in 96-well, flat-bottomed plates. SU5416 was serially diluted in media containing DMSO (<0.5%) and added to cultures of tumor cells 1 day after the initiation of culture. Cell growth was measured after 96 h using the sulforhodamine B method. IC50s were calculated by curve fitting using four-parameter analysis.|
|Concentrations||0, 0.05, 0.5, 5, 50 µm|
|Incubation time||96 h|
|Animal models||Female BALB/c nu/nu mice Intracolonic Xenograft Model|
|Dosages||25 mg/kg/day 50µl for 39 days|
|Administration||i.p. bolus injection|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points.
O'Donnell A, et al. Br J Cancer. 2005 Oct 17;93(8):876-83. PMID: 16222321.
Antiangiogenic effect by SU5416 is partly attributable to inhibition of Flt-1 receptor signaling.
Itokawa T, et al. Mol Cancer Ther. 2002 Mar;1(5):295-302. PMID: 12489845.
The angiogenesis inhibitor SU5416 has long-lasting effects on vascular endothelial growth factor receptor phosphorylation and function.
Mendel DB, et al. Clin Cancer Res. 2000 Dec;6(12):4848-58. PMID: 11156244.
SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types.
Fong TA, et al. Cancer Res. 1999 Jan 1;59(1):99-106. PMID: 9892193.
|Related VEGFR/PDGFR Products|
|Dovitinib (TKI-258) Dilactic Acid
Dovitinib Dilactic acid (TKI258 Dilactic acid) is the Dilactic acid of Dovitinib, which is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM.
|Toceranib(SU 11654; PHA 291639)
Toceranib(SU 11654; PHA 291639) is a kinase inhibitor with both antitumor and antiangiogenic activity through inhibition of KIT, vascular endothelial growth factor receptor 2, and PDGFRβ.
|Nintedanib (BIBF 1120)
Nintedanib (BIBF 1120) is a potent triple angiokinase inhibitor for 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 in cell-free assays. Phase 3.
AZD2932 is a potent and mutil-targeted protein tyrosine kinase inhibitor with IC50 of 8 nM, 4 nM, 7 nM, and 9 nM for VEGFR-2, PDGFRβ, Flt-3, and c-Kit, respectively.
Regorafenib 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.