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|Title:||INVESTIGATIONS OF INDOLEACRYLONITRILES AS ANTICANCER AGENTS||Authors:||SEE CHENG SHANG||Keywords:||Anticancer||Issue Date:||20-Jan-2017||Citation:||SEE CHENG SHANG (2017-01-20). INVESTIGATIONS OF INDOLEACRYLONITRILES AS ANTICANCER AGENTS. ScholarBank@NUS Repository.||Abstract:||Exploiting the relative biological differences between cancer cells and normal cells is the rationale underlying the therapeutic application of many anticancer drugs. Achieving elimination of cancer cells with minimal toxicity to normal tissues is a very much desired goal. Herein, the discovery of a novel compound P7, which induces cell death selectively in cancer cells while sparing normal cells, is described. This indoleacrylonitrile compound was found to act by a unique dual mode of action of disrupting autophagy and inducing mitotic dysfunction. Investigations into the SAR of P7 revealed key features in its structure that are essential for its dual properties. Investigational agents often suffer from poor solubility which severely limits their application. This was found to be the case with P7. Formulation studies led to a much-improved strategy for successful in vivo delivery of P7. Furthermore, a prodrug approach expanded the options available for oral delivery of active P7.||URI:||http://scholarbank.nus.edu.sg/handle/10635/135939|
|Appears in Collections:||Ph.D Theses (Open)|
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