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Global profiling of AMG510 modified proteins identified tumor suppressor KEAP1 as an off-target

ABSTRACT: Here, we presented a streamlined workflow to measure abundant AMG510 modified peptides including that of KRAS/G12C by direct profiling, and a pan-AMG510 antibody peptide IP workflow to profile less abundant AMG510 off-targets.

ORGANISM(S): Homo Sapiens

SUBMITTER: Jun Qin

PROVIDER: PXD029449 | iProX | Wed Jan 11 00:00:00 GMT 2023

REPOSITORIES: iProX

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Global profiling of AMG510 modified proteins identified tumor suppressor KEAP1 as an off-target.

Wang Yini Y Zhong Bowen B Xu Caixia C Zhan Dongdong D Zhao Songhao S Wu Hongxing H Liu Mingwei M Lan Xiaoling X Cai Danni D Ding Qian Q Zheng Biao B Lan Jiong J Lv Qiang Q Wang Yi Y Qin Jun J

iScience 20230128 2

KRAS inhibitor AMG510 covalently modifies the G12C residue and inactivates the KRAS/G12C function. Because there are many reactive cysteines in the proteome, it is important to characterize AMG510 on-target modification and off-targets. Here, we presented a streamlined workflow to measure abundant AMG510 modified peptides including that of KRAS/G12C by direct profiling, and a pan-AMG510 antibody peptide IP workflow to profile less abundant AMG510 off-targets. We identified over 300 off-target si ...[more]

PMID: 36824285

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