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The degradation mechanism follows a non-traditional, sequential process: the high-affinity KRAS G12C ligand first covalently engages its target, followed by covalent recruitment of the E3 ligase through the solvent-exposed electrophilic moiety

eLife 9 , e54166 (2020)

This combination preserves lean mass effectively during the weight loss phase

It acted via non-competitive inhibition, binding to non-active sites and inducing structural rearrangements, with reduced -helical content and increased -sheet and random coil, thereby disrupting ACE function without active-site competition

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