Anticancer agent 81 (Compound 37b3) induces tumor cell cycle arrest and apoptosis, and serves as a payload for conjugation with Trastuzumab, forming the antibody-drug conjugate (ADC) T-PBA, which retains Trastuzumab's targeting and internalization properties [1].

Anticancer agent 81 (Compound 37b3) exhibits cytotoxicity against SKOV3, MDA-MB-231, and NCI-N87 cells after 72 hours of exposure [1]. It induces DNA interstrand cross-linking at 0-5 µM [1], causes S-phase cell cycle arrest in SKOV3 cells at 0-3 nM over 24 hours, leading to apoptosis after 48 hours [1]. At a 25 nM dosage for 12 hours, it penetrates the nuclei of SKOV3 and MDA-MB-231 cells, targeting DNA [1]. Anticancer agent 81 triggers DDR signaling pathways via DNA cross-linking, activates the caspase cascade, and enhances PARP, resulting in cell cycle arrest and apoptosis [1], while 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.