Discovery platform for potent ADC payloads from marine sources

Marine organisms have emerged as an important source of biologically active small molecules, particularly for highly potent cytotoxins. Because of this potent bioactivity, the traditional small molecule, single agent drug discovery approach is severely hampered by a dose-limiting therapeutic window. However, the recent success of Antibody Drug Conjugates (ADC), which offers the targeted delivery of cytotoxins to tumor cells via antibody-binding, provides a renewed path for promising, potent, anti-cancer compounds. ADC's and similar targeting approaches are truly an enabling technology for natural products. In our ongoing drug discovery program, we have developed a unique ADC payload discovery platform which allows a rapid identification of marine-derived cytotoxic payloads. Using this technology, we have discovered potent ADC payloads. The discovery platform and initial results will be discussed.