Conventional chemotherapy is insufficient for precise cancer treatment due to its lack of selectivity and inevitable side effects. Targeted drugs have emerged as a promising solution for precise cancer treatment. A common strategy is to conjugate therapeutic agents with ligands that can specifically bind to tumor cells, providing targeted therapy. Similar to the more successful antibody drug conjugates (ADCs), small molecule drug conjugates (SMDCs) are another promising class of targeted drugs, consisting of three parts: targeting ligand, cleavable linker and payload. Compared to ADCs, SMDCs have the advantages of smaller size, better permeability, simpler preparation process and non-immunogenicity, making them a promising alternative to ADCs. This review describes the characteristics of the targeting ligand, linker and payload of SMDCs and the criteria for selecting a suitable one. We also discuss recently reported SMDCs and list some successful SMDCs that have entered clinical trials.
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