hUP1-IN-2 is a Urd-competitive and Pᵢ-noncompetitive hUP1 inhibitor with K i values of 68 nM and 127 nM, respectively. hUP1-IN-2 reduces the toxicity of 5-fluorouracil against colon cancer. hUP1-IN-2 can be used in the research of colon cancer [1].
In Vitro, hUP1-IN-2 (Compound 10a) at a concentration of 1 μM inhibits the catalytic activity of recombinant hUP1 by 80%[1]. hUP1-IN-2 acts as a competitive inhibitor of recombinant hUP1 against Urd (Ki = 68 nM), and a non-competitive inhibitor against Pᵢ (Ki = 127 nM)[1]. hUP1-IN-2 binds to free recombinant hUP1, the hUP1-Pi binary complex, and the hUP1-R1P binary complex via exothermic reactions, with the highest affinity for the hUP1-Pi complex (Kd = 151 nM)[1]. hUP1-IN-2 exhibits negligible inhibitory activity against thymidine phosphorylase, with an IC50 >100 μM[1]. hUP1-IN-2 (1-100 μM; 72 h) exerts no significant in vitro cytotoxicity against HaCat, HT-29 or SW-620 cells when applied at concentrations ranging from 1 to 100 μM for 72 h[1]. hUP1-IN-2 (30 μM; 72 h) does not alter the cytotoxicity of 5-FU in HaCat cells, reduces the cytotoxicity of 5-FU in HT-29 cells, and enhances the cytotoxicity of 5-FU in SW-620 cells[1].
References:
[1]. Renck D, et al. Design of novel potent inhibitors of human uridine phosphorylase-1: synthesis, inhibition studies, thermodynamics, and in vitro influence on 5-fluorouracil cytotoxicity. Journal of medicinal chemistry. 2013 Nov 14;56(21):8892-902.
In Vitro, hUP1-IN-2 (Compound 10a) at a concentration of 1 μM inhibits the catalytic activity of recombinant hUP1 by 80%[1]. hUP1-IN-2 acts as a competitive inhibitor of recombinant hUP1 against Urd (Ki = 68 nM), and a non-competitive inhibitor against Pᵢ (Ki = 127 nM)[1]. hUP1-IN-2 binds to free recombinant hUP1, the hUP1-Pi binary complex, and the hUP1-R1P binary complex via exothermic reactions, with the highest affinity for the hUP1-Pi complex (Kd = 151 nM)[1]. hUP1-IN-2 exhibits negligible inhibitory activity against thymidine phosphorylase, with an IC50 >100 μM[1]. hUP1-IN-2 (1-100 μM; 72 h) exerts no significant in vitro cytotoxicity against HaCat, HT-29 or SW-620 cells when applied at concentrations ranging from 1 to 100 μM for 72 h[1]. hUP1-IN-2 (30 μM; 72 h) does not alter the cytotoxicity of 5-FU in HaCat cells, reduces the cytotoxicity of 5-FU in HT-29 cells, and enhances the cytotoxicity of 5-FU in SW-620 cells[1].
References:
[1]. Renck D, et al. Design of novel potent inhibitors of human uridine phosphorylase-1: synthesis, inhibition studies, thermodynamics, and in vitro influence on 5-fluorouracil cytotoxicity. Journal of medicinal chemistry. 2013 Nov 14;56(21):8892-902.