TG 100572

• CAT Number: I005220
• CAS Number: 867334-05-2
• Molecular Formula: C26H26ClN5O2
• Molecular Weight: 475.97
• Purity: ≥95%
• Synonyms: 4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol
• Target: Src
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 2/7/2/1/0.5 nM (VEGFR1/VEGFR2/FGFR1/Src/Fyn) [1]

TG 100572 is a multi-targeted kinase inhibitor that inhibit select growth factor receptor tyrosine kinases and Src familt kinases with IC50 values of 2/7/2/1/0.5 nM for VEGFR1/VEGFR2/FGFR1/Src/Fyn kianse respectively.IC50 value: 2/7/2/1/0.5 nM (VEGFR1/VEGFR2/FGFR1/Src/Fyn) [1]Target: Multi-kianse; VEGFR/FGFR/PDGFR/Srcin vitro: TG100572 inhibited vascular endothelial cell proliferation in vitro (ED50= 610 ± 71 nM, mean ± SEM, N= 3) and blocked VEGF-induced phosphorylation of extracellular signal-regulated kinase (ERK), a signaling event in VEGF-induced mitogenesis. Additionally, TG100572 induced apoptosis in rapidly proliferating, but not quiescent, endothelial cell cultures [1]. TG100572 inhibits downstream molecules involved in the vascular endothelial growth factor (VEGF) signaling pathway resulted in markedly diminished levels of HSV-induced angiogenesis and significantly reduced the severity of SK lesions [2].in vivo: Mice that received daily intraperitoneal injections of TG100572 (5 mg/kg) developed smaller CNV lesions than those seen in vehicle-injected mice; measuring CNV area using image analysis techniques demonstrated a 40% reduction compared to the vehicle control group.TG100572-treated group also lost an average 11% of their body weight over the 14 day course of this study compared to the vehicle-treated group which gained an average 1%. This weight loss suggests at least some degree of systemic toxicity, in agreement with our starting hypothesis that achieving acceptable therapeutic indices will be challenging with systemic delivery of multi-targeted kinase inhibitors [1].

Reference

[1]. Doukas, John; Mahesh, Sankaranarayana; Umeda, Naoyasu et al. Topical administration of a multi-targeted kinase inhibitor suppresses choroidal neovascularization and retinal edema. Journal of Cellular Physiology (2008), 216(1), 29-37.
[2]. Sharma S, et al. An anti-inflammatory role of VEGFR2/Src kinase inhibitor in herpes simplex virus 1-induced immunopathology. J Virol. 2011 Jun;85(12):5995-6007.