Organic Chemistry Seminar – Joseph Pacheco

About the event

Speaker: Joseph Pacheco

Research Group: Berkman

Title: The first ADC bearing the ferroptosis inducer RSL3 as a payload with conservation of the fragile electrophilic warhead

Abstract: Ferroptosis is an iron-dependent non-apoptotic form of programmed cell death. Since its naming in 2012, the underlying mechanisms of ferroptosis have been further elucidated and this form of programmed cell death has shown great potential for the treatment of diseases such as cancer. As such, ferroptosis has been increasingly researched on various cancer cell lines. Several inducers of ferroptosis have been identified and are often used in research to further understand relevant biochemical pathways and its effectiveness in treating different types of cancer. This research paper focuses on a new antibody drug conjugate (ADC) that utilizes an analogue of the known ferroptosis inducer RAS-selective lethal 3 (RSL3) and attaching it to an antibody drug conjugate via peptide bonding. Simultaneously, trastuzumab is the chosen monoclonal antibody for the ADC which then binds to the HER2 receptors on the BT-474 cell line of human breast cancer. This paper thus explains the synthesis of the ADC and its effectiveness on the BT-474 cell line. Administration of the chemotherapeutic drug doxorubicin and its effectiveness in combination with and without the RSL3-ADC is also interpreted.

This talk will summarize ferroptosis and highlight the organic synthesis of the ADC and its effectiveness in a combination therapy that utilizes both targeted drug therapy and ferroptosis. Through this research, a novel and more precise form of cancer therapy can be made a possibility.