Naturally occurring compounds have historically provided a rich source of successful drug treatments for cancer. In fact, several of Nature's chemical harvests have been directly developed into life-saving chemotherapies without chemical modification such as paclitaxel that is recognized on the World Health Organization's (WHO) list of essential medicines. However, the direct preclinical development of most natural products, even those with promising anti-cancer activities, remains a formidable challenge due to significant hurdles that impede the drug discovery process. Most significant of these hurdles is the lack of early drug supplies due to low natural abundance or complex chemical struc...

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Naturally occurring compounds have historically provided a rich source of successful drug treatments for cancer. In fact, several of Nature's chemical harvests have been directly developed into life-saving chemotherapies without chemical modification such as paclitaxel that is recognized on the World Health Organization's (WHO) list of essential medicines. However, the direct preclinical development of most natural products, even those with promising anti-cancer activities, remains a formidable challenge due to significant hurdles that impede the drug discovery process. Most significant of these hurdles is the lack of early drug supplies due to low natural abundance or complex chemical structures that makes the manufacture of these compounds difficult at the earliest stages of drug discovery. This study will evaluate newly designed small molecules inspired by the taccalonolides, a novel natural product class of promising anticancer compounds, that will be amendable to rapid preclinical development as potential new therapies for the treatment of women's cancers. We will use a combination of modern computational approaches and machine learning capabilities to design simplified drug-like compounds that use the structure of the taccalonolides as an architectural blueprint for our design. In turn, we will synthesize these rationally designed compounds in our laboratories that will undergo a battery of preclinical testing to identify the best leads as potential new treatments for women's cancers including ovarian, breast, and cervical cancers. This project will benefit from an existing synergistic collaboration between two research groups at the interface of chemistry and biology with over 10 years of successful development of anticancer compounds.

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