Description
KIN59 is a purine riboside derivative that allosterically inhibits thymidine phosphorylase (TPase; IC
50s = 44 and 67 μM for purified
E. coli and human enzymes, respectively). Through this action, KIN59 blocks the conversion of thymidine to thymine. KIN59 inhibits TPase-induced angiogenesis in a chicken chorioallantoic membrane assay and reduces endothelial cell migration without impacting proliferation. KIN59 also inhibits the binding of fibroblast growth factor 2 (FGF2) to FGF receptor 1, preventing the growth and neovascularization of subcutaneous tumors induced by FGF2-transformed endothelial cells injected in immunodeficient nude mice.
Uses
5’O-Tritylinosine acts as an allosteric inhibitor of angiogenic enzyme thymidine phosphorylase.
Uses
5’-O-Tritylinosine acts as an allosteric inhibitor of angiogenic enzyme thymidine phosphorylase.
in vivo
KIN59 (15 mg/kg; s.c.; twice daily from day 2 for 20 days) shows anti-tumor activity in mice[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. |
References
[1] SANDRA LIEKENS. The nucleoside derivative 5’-O-trityl-inosine (KIN59) suppresses thymidine phosphorylase-triggered angiogenesis via a noncompetitive mechanism of action.[J]. The Journal of Biological Chemistry, 2004, 279 28: 29598-29605. DOI:
10.1074/jbc.m402602200[2] SANDRA LIEKENS. 5’-O-tritylated nucleoside derivatives: inhibition of thymidine phosphorylase and angiogenesis.[J]. Molecular Pharmacology, 2006, 70 2: 501-509. DOI:
10.1124/mol.105.021188[3] SANDRA LIEKENS. The thymidine phosphorylase inhibitor 5’-O-tritylinosine (KIN59) is an antiangiogenic multitarget fibroblast growth factor-2 antagonist.[J]. Molecular Cancer Therapeutics, 2012, 11 4: 817-829. DOI:
10.1158/1535-7163.mct-11-0738
