KIN-59

KIN59, the purine riboside derivative, is a noncompetitive inhibitor against human and bacterial recombinant TPase [1]. TPase is an enzyme with an important role in the pyrimidine nucleoside salvage pathway and the inactivation of cytotoxic pyrimidine nucleoside analogues. TPase also recognizes several nucleoside analogues clinically used as antiviral or anti-tumor agents [1]. Overexpression of TPase has been observed in many solid tumors [1].

In vitro: In the purified E. coli and human TPase, KIN59 inhibited the E. coli and human TPases in a reversible or irreversible manner, with the IC50 of 44 ± 3 and 67 ± 20 M, respectively. KIN59 was a potent inhibitor of E. coli TPase with Ki values of 39 M against dThd and 146 M against phosphate, resulting in Ki /Km values of 0.039 and 0.10, respectively. KIN59 induced the formation of an avascular area around and inside the sponge. In the CAM assay, KIN59 completely prevented TPase-stimulated blood vessel formation, without any visible side effects [1]. KIN59 was active against TPase-induced angiogenesis in the chorioallantoic membrane assay [1].

Reference:
[1] Liekens S, Hernández A I, Ribatti D, et al.  The nucleoside derivative 5′-O-trityl-inosine (KIN59) suppresses thymidine phosphorylase-triggered angiogenesis via a noncompetitive mechanism of action[J]. Journal of Biological Chemistry, 2004, 279(28): 29598-29605.