Affinity-based protein profiling reveals cellular targets of photoreactive anticancer inhibitors

Abstract

Affinity-based protein profiling has proven to be a powerful method in target identification of bioactive molecules. Here, this technology was applied in two photoreactive anticancer inhibitors, arenobufagin and HM30181. Using UV irradiation, these photoreactive reagents can covalently cross-link to target proteins, leading to a covalent binding with target proteins. Moreover, the cellular on/off targets of these two molecules, including ATP1A1, MDR1, PARP1, DDX5, NOP2, RAB6A, and ERGIC1 were first identified by affinity-based protein profiling and bioimaging approaches. The protein hit, PARP1, was further validated to be involved in the function of the anticancer effects.

Ke Cheng, PhD

I am a chemical biologist with expertise in organic chemistry, bioconjugation, protein biology, and oncology. My research focuses on developing small molecule probes and drugs, antibody drug conjugates, and radioligand agents for targeted cancer therapy, including the design of cleavable ADC linkers and next generation payloads, as well as tumor activatable probes and chemoproteomics driven target discovery.