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Cytotoxic agents and Antibody-drug Conjugates

 Drug name  Target  Mode of Action  Example
Auristatins α-Tubulin Prevent tubulin polymerization
Maytansinoids α-Tubulin Prevent tubulin polymerization
Calicheamicins Sequence-specific minor groove of DNA Causes double-strand DNA breaks
Duocarmycin analogues Bind to specific minor groove of DNA Break down adenine-specific molecules in the DNA structure
Doxorubicin and Doxorubicin derivatives Topoisomerase II
DNA complexes
Inhibit DNA religation, leading to DNA double-strand breaks
  • BR96-DOX
CC-1065 Sequence-specific minor groove of DNA Induces adenine alkylation
Anthracyclines DNA, RNA complexes Inhibit DNA and RNA synthesis by intercalating between base pairs, preventing replications
Pyrrolobenzodiazepine Sequence-selective. Bind to the minor groove of DNA and covalently attach to guanine residues

Interfere with the action of endonuclease enzymes on DNA and block transcription by inhibiting DNA polymerase in a sequence specific manner

Other cytotoxic agents used in the development of antibody-drug conjugates include:

  • Streptonigtin (anti CD30 and anti CD70)
  • Geldanamycin (HSP90 inhibitor)
  • Centanamycin (ML-970; indolecarboxamide);
  • SN38 is the active metabolite of irinotecan (an analog of Camptothecin, a topoisomerase I inhibitor)

Last Editorial Review: March 19, 2015

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