Anticancer agent 81 (Compound 37b3) induces tumor cell cycle arrest and apoptosis and serves as a payload for conjugation with Trastuzumab, resulting in the antibody-agent conjugate (ADC) T-PBA. T-PBA retains the targeting and internalization properties of Trastuzumab [1].

Anticancer agent 81 (Compound 37b3) demonstrates cytotoxic effects on SKOV3, MDA-MB-231, and NCI-N87 cells after 72 hours of exposure [1]. It induces DNA interstrand cross-linking at concentrations ranging from 0 to 5 µM [1] and causes S-phase cell cycle arrest in SKOV3 cells at 0-3 nM concentrations over 24 hours, leading to apoptosis after 48 hours [1]. At a 25 nM dosage for 12 hours, this compound penetrates the nuclei of SKOV3 and MDA-MB-231 cells, targeting DNA [1]. Furthermore, Anticancer agent 81 triggers DDR signaling pathways through DNA cross-linking, subsequently activating the caspase cascade and PARP, which results in cell cycle arrest and apoptosis [1]. The compound also forms covalent bonds with DNA sequences, predominantly interacting with the major groove of DNA [1].

Administered intravenously at doses of 1-10 mg/kg every three days for a total of four doses, T-PBA markedly inhibited tumor progression in two Her2-positive mouse xenograft models, demonstrating superior efficacy to Trastuzumab [1] with no apparent toxicity or adverse effects.