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| Field | Value |
| Title | Small Molecules Inspired by the Natural Product Withanolides as Potent Inhibitors of Wnt Signaling |
| Names |
SHEREMET, M
KAPOOR, S SCHRODER, P KUMAR, K ZIEGLER, S WALDMANN, H |
| Date Issued | 2017 (iso8601) |
| Abstract | Wnt signaling is a fundamental pathway that drives embryonic development and is essential for stem cell maintenance and tissue homeostasis. Dysregulation of Wnt signaling is linked to various diseases, and a constitutively active Wnt pathway drives tumorigenesis. Thus, disruption of the Wnt response is deemed a promising strategy for cancer drug discovery. However, only few clinical drug candidates that target Wnt signaling are available so far, and new small-molecule modulators of Wnt-related processes are in high demand. Here we describe the synthesis of small molecules inspired by withanolide natural products by using a pregnenolone-derived -lactone as the key intermediate that was transformed into a -lactone appended to the D-ring of the steroidal scaffold. This natural-product-inspired compound library contained potent inhibitors of Wnt signaling that act upstream of the destruction complex to stabilize Axin in a tankyrase-independent manner. |
| Genre | Article |
| Topic | WNT/BETA-CATENIN PATHWAY |
| Identifier | CHEMBIOCHEM,18(18)1797-1806 |