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Anticancer Agents for Triple-Negative Breast Cancers
University of Florida
Small molecule
Oncology
Hit To Lead or Lead Optimization
• These first-in-class anticancer agents could be useful against cell proliferative disorders, specifically breast and other cancers which are modulated by HER2/HER3/EGFR genes.
• The compounds use optimal disulfide disrupting agents to disrupt extracellular disulfide bonds associated with the oncogenic functions of the EGFR, HER2, and HER3 proteins. Disulfide bond disrupting agents are expected to be toxic to cancer cells dependent on HER2 or EGFR for proliferation and survival but are well tolerated by normal tissues.
• The DDAs appear to selectively kill EGFR+, HER2+ and MYC+ breast cancer cells through induction of ER stress and potentiation of TRAILmediated cell death. Unlike cancer treatments using HER2-targeted antibodies (e.g., Trastuzumab and Pertuzumab), this compound simultaneously inactivates EGFR, HER2, and HER3, instead of the single receptor, HER2. This decreases a tumor's ability to develop primary resistance to the anticancer agent.
US20210147379A1
