Antiparasitic agent-30 is a potent adenosine kinase TbrAK modulator and antitrypanosomal agent. Antiparasitic agent-30 exhibits significant inhibitory activity against Trypanosoma brucei rhodesiense, while enhancing the activity of recombinant TbrAK ( EC 50 =38 nM, K a =75 nM-497 nM). Antiparasitic agent-30 exerts its pharmacological effects by eliminating intrinsic substrate inhibition and hyperactivating TbrAK in Trypanosoma brucei rhodesiense. Antiparasitic agent-30 serves as a valuable tool molecule for studying acute African human trypanosomiasis (sleeping sickness) [1].
In Vitro, Antiparasitic agent-30 (Compound 1) potently inhibits the viability of T. b. rhodesiense parasites, with an IC50 of 1.0 μM[1]. Antiparasitic agent-30 (1-750 μM; 10 min) enhances the activity of recombinant TbrAK in a concentration-dependent manner, with an EC50 of 38.9 μM, and increases the activity by 2.5-fold at 50 μM[1]. Antiparasitic agent-30 enhances the activity of recombinant TbrAK in radiometric assays, with a highly potent EC50 of 38 nM[1]. Antiparasitic agent-30 (150 μM) binds to two distinct sites of recombinant TbrAK (7 μM), and exhibits high affinity for the primary binding site (Kd=75 nM)[1]. Antiparasitic agent-30 exhibits reduced potency against T. b. brucei parasites with silenced TbAK, with its IC50 increasing from 131 nM to 271 nM, confirming that its activity depends on the expression of adenosine kinase[1].
References:
[1]. Kuettel S, et al. Adenosine Kinase of T. b. rhodesiense identified as the putative target of 4-[5-(4-phenoxyphenyl)-2 H-pyrazol-3-yl] morpholine using chemical proteomics[J]. PLoS neglected tropical diseases, 2009, 3(8): e506.
In Vitro, Antiparasitic agent-30 (Compound 1) potently inhibits the viability of T. b. rhodesiense parasites, with an IC50 of 1.0 μM[1]. Antiparasitic agent-30 (1-750 μM; 10 min) enhances the activity of recombinant TbrAK in a concentration-dependent manner, with an EC50 of 38.9 μM, and increases the activity by 2.5-fold at 50 μM[1]. Antiparasitic agent-30 enhances the activity of recombinant TbrAK in radiometric assays, with a highly potent EC50 of 38 nM[1]. Antiparasitic agent-30 (150 μM) binds to two distinct sites of recombinant TbrAK (7 μM), and exhibits high affinity for the primary binding site (Kd=75 nM)[1]. Antiparasitic agent-30 exhibits reduced potency against T. b. brucei parasites with silenced TbAK, with its IC50 increasing from 131 nM to 271 nM, confirming that its activity depends on the expression of adenosine kinase[1].
References:
[1]. Kuettel S, et al. Adenosine Kinase of T. b. rhodesiense identified as the putative target of 4-[5-(4-phenoxyphenyl)-2 H-pyrazol-3-yl] morpholine using chemical proteomics[J]. PLoS neglected tropical diseases, 2009, 3(8): e506.