| Description | TAS1553 is a highly effective, orally bioavailable protein-protein interaction (PPI) inhibitor with an IC50 value of 0.0396 μM. It effectively hinders DNA replication and diminishes the intracellular dATP pool. Moreover, TAS1553 induces apoptosis, making it a valuable compound in cancer research [1]. |
| In vitro | TAS1553（0.001-1 μM）剂量依赖性地抑制了RNR的酶活性[1]。TAS1553（3天）对固态和血液来源的人类癌症细胞系具有抗增殖活性，GI 50值范围为0.228至4.15 μM[1]。TAS1553（1-10 μM；0-2小时；HCC38和MV-4-11细胞）以剂量和时间依赖的方式减少了细胞内dATP水平，这是DNA复制的关键代谢物[1]。TAS1553（0-10 μM；0-24小时；HCC38和MV-4-11细胞）以剂量和时间依赖的方式诱导复制压力和凋亡[1]。西方印迹分析[1]细胞系：HCC38和MV-4-11细胞；浓度：0，0.1，0.3，1，3及10 μM；孵育时间：0，1，2，4，8及24小时；结果显示Ser345、Ser4、Ser8和Thr21磷酸化水平的表达增加，裂解PARP和裂解caspase-3的水平增加。 |
| In vivo | TAS1553 (25-200 mg/kg; p.o.; 24小时; 雌性F344/NJcl-rnu/rnu大鼠及BALB/cAJcl-nu/nu小鼠)体内显示RNR抑制效果[1]。TAS1553 (50-200 mg/kg; p.o.; 每日, 15天; 雌性F344/NJcl-rnu/rnu大鼠及BALB/cAJcl-nu/nu小鼠)体内具有抗肿瘤活性[1]。实验动物模型: 雌性F344/NJcl-rnu/rnu大鼠和BALB/cAJcl-nu/nu小鼠[1]。给药剂量: 25, 50, 100和200 mg/kg。给药方式: 口服，24小时。结果: 减少细胞内dATP池，诱导复制应激和凋亡。实验动物模型: 雌性F344/NJcl-rnu/rnu大鼠和BALB/cAJcl-nu/nu小鼠[1]。给药剂量: 50, 100和200 mg/kg。给药方式: 每日口服，持续15天。结果: 处理组/对照组的肿瘤生长抑制率分别为52.0% (50 mg/kg)、45.0% (100 mg/kg)和29.4% (200 mg/kg)。 |
| molecular weight | 482.91 |
| Molecular formula | C20H20ClFN4O5S |
| CAS | 2166023-31-8 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | DMSO: 90 mg/mL (186.4 mM), Sonication is recommended. |
| References | 1. Ueno H, et, al. TAS1553, a small molecule subunit interaction inhibitor of ribonucleotide reductase, exhibits antitumor activity by causing DNA replication stress. Commun Biol. 2022 Jun 9;5(1):571. |