5’O-Tritylinosine

KIN59 (5’-O-Tritylinosine) is a potent thymidine phosphorylase allosteric inhibitor. KIN59 inhibits FGF2-stimulated cell growth. KIN59 inhibits the expression of p-FGFR1, P-Akt in FGF2 (10 ng/mL) stimulated cells. KIN59 shows anti-tumor activity[1].

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Nucleoside Antimetabolite/Analog

KIN59 (0-100 µM; 24 h) 抑制细胞增殖，对 FGF2 (30 ng/mL) 和 PBS (10%) 刺激的 GM7373 细胞的 IC50 值分别为 5.8 和 63 µM[1]. KIN59 (60 µM; 30 min) 抑制 FGF2 （10 ng/mL）刺激的 FGFR1 过表达 GM7373-FGFR1 细胞中 p-FGFR1、P-Akt 的表达[1]。KIN59 抑制重组细菌 (大肠杆菌) 和人胸苷磷酸化酶 (TPase)，IC50 值分别为 44 μM 和 67 μM[2]。 Cell Proliferation Assay[1] Cell Line: GM7373 cells Concentration: 0-100 µM Incubation Time: 24 h Result: Inhibited FGF2 (30 ng/mL)-induced proliferation of bovine macrovascular endothelial GM7373 cells in a dose-dependent manner with IC50 values of 5.8, 63 µM for FGF2 and PBS, respectively. Western Blot Analysis[1] Cell Line: GM7373-FGFR1, GM7373-VEGFR2 cells Concentration: 60 µM Incubation Time: 30 min Result: Inhibited FGFR1 phosphorylation and Akt activation triggered by FGF2 in FGFR1-overexpressing GM7373-FGFR1 cells, showed minor inhibits on VEGF-mediated VEGFR2 phosphorylation and Akt activation in GM7373 cells overexpressing VEGFR2.

KIN59 (15 mg/kg；皮下注射；从第 2 天开始每天两次，持续 20 天) 在小鼠体内显示出抗肿瘤活性[1]。 Animal Model: Eight-week-old female, 25 g, athymic, nude nu/nu mice (F2T-luc2.9 cellss)[1] Dosage: 15 mg/kg Administration: S.c.; twice daily from day 2 (once daily during the weekend) at a site distant from the tumor (inoculation) site for 20 days Result: Caused a significant inhibition in the rate of tumor growth.

[1]. Liekens S, et al. The thymidine phosphorylase inhibitor 5'-O-tritylinosine (KIN59) is an antiangiogenic multitarget fibroblast growth factor-2 antagonist. Mol Cancer Ther. 2012 Apr;11(4):817-29.  

[2]. Liekens S, et al. Thymidine phosphorylase is noncompetitively inhibited by 5'-O-trityl-inosine (KIN59) and related compounds. Nucleosides Nucleotides Nucleic Acids. 2006;25(9-11):975-80.