Antibody–drug conjugates (ADCs) have become an important class of targeted anticancer therapeutics by integrating the tumor selectivity of monoclonal antibodies with the potent cytotoxicity of small-molecule payloads through rational linker design. This review summarizes the structural fundamentals of ADCs, including antibodies, linkers, and payloads, and describes their coordinated mechanism of action. We trace the evolutionary trajectory of ADCs across three generations, highlighting key breakthroughs, limitations, and representative agents for each era. Furthermore, we elaborate on cleavage mechanisms of linkers (cleavable and non-cleavable). We also categorize and discuss cytotoxic payloads, covering traditional microtubule-disrupting agents, DNA-damaging agents, and novel mechanism-based payloads, along with their modification strategies and preclinical/clinical performance. Finally, we discuss representative and clinically influential ADC designs, with emphasis on the relationships among antibody, linker, and payload.

Leonurus japonicus Houtt is an exceptional medicinal herb used to treat obstetrical and gynecological diseases in traditional Chinese medicine, and it has significant effects on the treatment of dysmenorrhea and postpartum hemorrhage. This study investigated the effects of coumarins with diverse substituent groups from L. japonicus on isolated uterine smooth muscle and the preliminary mechanism of the most effective compound. Eight coumarins isolated from L. japonicus were assessed for their effects on the isolated uterine smooth muscle of nonpregnant rats in vitro. Coumarins 1 and 2 significantly promoted the contraction of rat uterine smooth muscle strips, whereas coumarins 3–5 showed remarkable relaxing effects against oxytocin (OT)-induced rat uterine smooth muscle contraction. Further mechanism investigations revealed that bergapten (coumarin 1) significantly increased the level of Ca²⁺ in uterine tissues by promoting extracellular Ca²⁺ influx and intracellular Ca²⁺ release, which were related to the activation of L-type Ca²⁺ channels and α-receptors. By contrast, osthole (coumarin 5), an α receptor antagonist, inhibited OT-induced uterine smooth muscle contraction by decreasing the level of Ca²⁺ in uterine tissues via inhibition of extracellular Ca²⁺ influx and intracellular Ca²⁺ release. This study demonstrates that the coumarins from L. japonicus are effective substances for regulating uterine smooth muscle contraction, but different coumarins with diverse substituent groups have different, even opposite effects. It can be inferred that coumarins are closely related to the efficacy of L. japonicus in the treatment of dysmenorrhea and postpartum hemorrhage.

One new pyridinone alkaloid pseudogymnone A (1) and one new tricyclic polyketide penijanthinone C (2), together with six known compounds, harzianic acid (3), 3-methyl-2-(2-nonenyl)-4(1H)-quinolinone (4), emodic acid (5), alaternin (6), violaceol-I (7), and violaceol-II (8), were obtained from the Cordyceps-colonizing fungus Pseudogymnoascus roseus. The structures and absolute configurations of the isolated compounds were elucidated through a combination of NMR and MS spectroscopic analyses, ECD calculations, and X-ray crystallography. Compound 3 exhibited obvious cytotoxicity against A549 (IC₅₀ = 4.2 µM) and MGC (IC₅₀ = 3.8 µM) cell lines. Integrated network pharmacology and molecular docking analyses indicated that compound 3 exerts potential anti-gastric-cancer effects by modulating multiple cancer-related signaling pathways, with EGFR identified as a potential target of compound 3.