Tumor cell targets of the activated small-molecule drug

The term 'Tumor cell targets of the activated small-molecule drug' refers to the intracellular molecular targets of cytotoxic payloads released from small-molecule drug conjugates (SMDCs), antibody-drug conjugates (ADCs), or conditionally activated prodrugs. These payloads are typically potent cytotoxic agents that are chemically modified or conjugated to a targeting moiety to remain inactive during systemic circulation. Upon reaching the tumor microenvironment or being internalized by tumor cells, the 'activated' (released) small-molecule drug binds to its specific targets, such as Topoisomerase I/II, DNA, or Tubulin. This targeted delivery mechanism is designed to maximize the concentration of the active drug at the tumor site while minimizing damage to healthy tissues. Common examples include the release of Doxorubicin from Legubicin to target Topoisomerase II or the release of Auristatins to target microtubules. The activation process often involves enzymatic cleavage of a linker by tumor-enriched proteases like legumain or cathepsins. Once released, the small-molecule drug exerts its therapeutic effect by disrupting critical cellular functions, leading to apoptosis and tumor regression. This approach allows for the use of highly toxic molecules that would otherwise be too dangerous for systemic administration. The efficacy of these drugs depends on both the successful targeting of the conjugate and the presence of the intracellular target in the tumor cells.

Other names

Intracellular payload targetsCytotoxic payload targetsTargets of released small-molecule drugs

Selective delivery and release of a cytotoxic payload that inhibits essential intracellular processes such as DNA replication, topoisomerase activity, or microtubule assembly.