H3B-120 is a highly selective, competitive and allosteric carbamoyl phosphate synthetase 1 (CPS1) inhibitor with an IC50 of 1.5 μM and a Ki of 1.4 μM. H3B-120 has anti-cancer activity[1].
Carbamoyl phosphate synthetase 1 (CPS1) catalyzes the first step in the ammonia-detoxifying urea cycle, converting ammonia to carbamoyl phosphate under physiologic conditions. In cancer, CPS1 overexpression supports pyrimidine synthesis to promote tumor growth in some cancer types, while in others CPS1 activity prevents the buildup of toxic levels of intratumoral ammonia to allow for sustained tumor growth.
H3B-120 is a highly selective, competitive and allosteric carbamoyl phosphate synthetase 1 (CPS1) inhibitor with an IC50 of 1.5 μM and a Ki of 1.4 μM. H3B-120 has anti-cancer activity. H3B-120 has no inhibition of CPS2 activity of CAD (CPS2, aspartyl transcarbamylase, dihydroorotase). H3B-120 achieves inhibition by binding to an allosteric pocket situated between the integrating and ATP A domains. H3B-120 (25, 50, 75, 100 μM) inhibits urea production in a dose-dependent manner, although the cellular potency decreases significantly compared with enzymatic assays. The half-life of H3B-120 is only 40 min[1]. Treatment of human hepatocytes with H3B-120 decreased urea release into conditioned media. Stable-isotope tracer experiments using 15N-labeled ammonia in the presence or absence of H3B-120 revealed that H3B120 blocked labeling of pyrimidines but had no effect on purines. H3B-120 could inhibit cellular CPS1 activity related to ammonia conversion to urea and subsequent pyrimidine synthesis[2].
搜索
