Pancreatic ductal adenocarcinoma (PDAC) is a particularly aggressive form of pancreatic cancer. It is difficult to treat due to the lack of early-stage biomarkers and the challenges of late-stage surgical and pharmaceutical treatment. The Lin28b/pre-let-7 interaction has been elucidated as a promising target, as it leads to downstream oncogene expression. Lin28b has a binding pocket and is not expressed in healthy adult cells, making it an ideal candidate for small-molecule inhibition.<br/>In-silico modeling has identified promising small-molecule targets that are analogues of a previously synthesized small-molecule inhibitor. Upon synthesis, these novel targets will be testing using isothermal calorimetry (ITC) to examine their binding. Through a further collaboration, these targets will eventually be tested ex vivo in human PDAC cell lines. Through this work, we hope to further elucidate the mode of binding of these inhibitors and put forward novel, effective inhibitors of the Lin28n/pre-let-7 interaction.

Targeting the Lin28b/pre-let-7 interaction in pancreatic ductal adenocarcinoma: Synthesis and <i>in vitro</i> testing of small-molecule inhibitors

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

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Targeting the Lin28b/pre-let-7 interaction in pancreatic ductal adenocarcinoma: Synthesis and in vitro testing of small-molecule inhibitors