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Potent Agelastatin Derivatives as Modulators for Cancer Invasion and Metastasis
Massachusetts Institute of Technology
Small molecule
Oncology
Hit To Lead or Lead Optimization
• AgA and AgE block metastasis by abrogating Tiam1-osteopontin.
• This technology is a panel of agelastatin A (AgA) and agelastatin E (AgE) derivatives with anti-metastatic properties. AgA and AgE block metastasis by abrogating Tiam1-osteopontin induced epithelial to mesenchymal transition (EMT), which is a key step in the metastasis of many cancers.
• AgA and AgE derivatives are highly effective in preventing breast cancer migration in in vivo assays at concentrations far below levels that are cytotoxic. In mouse breast cancer xenotransplantation studies AgA and AgE have no effect on primary tumor growth; however, strikingly, they block nearly all metastatic spread.
• Importantly, osteopontin has a pro-metastatic role in many other cancer types, suggesting that AgA/E may be generalizable antimetastasis drugs for other cancer indications. The pre-clinical data all indicate that AgA and AgE are promising anti-metastasis drug candidates.
US20200062771A1
Synthesis and Evaluation of Agelastatin Derivatives as Potent Modulators for Cancer Invasion and Metastasis. J Org Chem. (2017)
