Article
An engineered chimeric toxin that cleaves activated mutant and wild-type RAS inhibits tumor growth.
Proceedings of the National Academy of Sciences of the United States of America - 21 Jul 2020
Vidimar Vania, Beilhartz Greg L, Park Minyoung, Biancucci Marco, Kieffer Matthew B, Gius David R, Melnyk Roman A, Satchell Karla J F
Abstract excerpt
Despite nearly four decades of effort, broad inhibition of oncogenic RAS using small-molecule approaches has proven to be a major challenge. Here we describe the development of a pan-RAS biologic inhibitor composed of the RAS-RAP1-specific endopeptidase fused to the protein delivery machinery of diphtheria toxin. We show that this engineered chimeric toxin irreversibly cleaves and inactivates intracellular RAS at...
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