Breaking down KRAS: small-molecule degraders for cancer therapy
Tina Šket, Dieter Saur
Abstract
In their recently published study in Science , Popow and colleagues developed a proteolysis-targeting chimera (PROTAC) for the in vivo degradation of several oncogenic KRAS variants. 1 Leveraging detailed biophysical analyses and crystal structures of ternary complexes of candidate ligands for KRAS and the von Hippel-Lindau (VHL) E3 ubiquitin ligase complex, they designed a small molecule capable of potently and selectively targeting 13 of the 17 most common KRAS mutants.
Topics & Concepts
KRASComputational biologyCancer therapyCancerCancer researchMedicineBiologyInternal medicineColorectal cancerProtein Degradation and InhibitorsUbiquitin and proteasome pathwaysHistone Deacetylase Inhibitors Research