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].

TAS1553, within a concentration range of 0.001-1 μM, inhibits the enzymatic activity of RNR dose-dependently. At a concentration administered for three days, TAS1553 exhibits anti-proliferative effects against various solid and hematological human cancer cell lines, with GI50 values spanning from 0.228 to 4.15 μM. In experiments involving HCC38 and MV-4-11 cells, TAS1553 (1-10 μM; over 0-2 hours) significantly decreases the intracellular dATP pool, essential for DNA replication, in both a dose- and time-dependent manner. Furthermore, at concentrations ranging from 0 to 10 μM and over a period of 0 to 24 hours, TAS1553 induces replication stress and apoptosis in HCC38 and MV-4-11 cells, showcasing a dependence on both dosage and time. Western Blot Analysis reveals that, across varying concentrations (0, 0.1, 0.3, 1, 3, and 10 μM) and incubation times (0, 1, 2, 4, 8, and 24 hours), there is an increase in the phosphorylation of Ser345, Ser4, Ser8, and Thr21. Additionally, these conditions result in the increased levels of cleaved PARP and cleaved caspase-3, signaling enhanced apoptosis in the tested cell lines.

TAS1553, administered orally at doses ranging from 25-200 mg/kg for 24 hours, exhibits ribonucleotide reductase (RNR) inhibitory effects in female F344/NJcl-rnu/rnu rats and BALB/cAJcl-nu/nu mice, as evidenced by reduced intracellular dATP pools, induction of replication stress, and apoptosis [1]. Further, when given daily at dosages of 50-200 mg/kg for 15 days, it demonstrates significant antitumor activity, with tumor growth inhibition rates in the treated versus control group being 52.0% at 50 mg/kg, 45.0% at 100 mg/kg, and 29.4% at 200 mg/kg, respectively [1]. These findings underline the compound's potential in cancer therapeutics through both its inhibitory action on RNR and its capacity to reduce tumor growth effectively in vivo.