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- W2980467534 abstract "Abstract For over three decades, K-RAS has been known as the holy grail of cancer targets, one of the most frequently mutated oncogenes in cancer. Because the development of conventional small molecule K-RAS inhibitors has been extremely challenging, K-RAS has been dubbed as an undruggable target, and only recently a mutation specific inhibitor has reached clinical trials. Targeted protein degradation has emerged as a new modality in drug discovery to tackle undruggable targets. However, no degrader for K-RAS has been described thus far. Our laboratory has developed an Affinity-directed PROtein Missile (AdPROM) system for targeted proteolysis of endogenous proteins through the ubiquitin proteasome system. Here, we show that we can achieve degradation of endogenous K-RAS and H-RAS in different cell lines in a targeted manner using our AdPROM system. Our findings imply that endogenous RAS proteins can be targeted for proteolysis, thereby offering tantalising possibilities for an alternative therapeutic approach to these so-called undruggable targets in cancer." @default.
- W2980467534 created "2019-10-25" @default.
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- W2980467534 date "2019-10-16" @default.
- W2980467534 modified "2023-09-27" @default.
- W2980467534 title "Targeting endogenous K-RAS for degradation through the affinity-directed protein missile system" @default.
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- W2980467534 doi "https://doi.org/10.1101/805150" @default.
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