Page 10 - I. Chemical biology and drug discovery

[I. Chemical biology and drug discovery-5]

Elucidation of resistance and its mechanism of RTKi by

identifying new target protein

Tae Young Kim¹˙*, Eunsun Ji², Jinyoung Kim², Jongshin Yoo², Marcell Szasz³, Gyorgy Marko-Varga⁴,
Hojeong Kwon¹˙#

¹Biotechnology, Chemical Genomics Global Research Laboratory in yonsei university, Seoul 03722, Korea,

²Biomedical Omic Research Group, Korea Basic Science Institute, Chungbuk 28119, Korea, ³MTA-TTK Lendület
Cancer Biomarker Research Group, National Koranyi Institute of Pulmonology, Budapest 1117, Hungary,
⁴Biomedical Engineering, Clinical Protein Science & Imaging, Lund SE22184, Sweden

Receptor Tyrosine Kinase Inhibitor (RTKi) was widely known to inhibit the kinase activity of Epithelial Growth Factor
Receptor (EGRF) and to treat Non-Small Cell Lung Cancer (NSCLC) patients. Although high efficacy on NSCLC, it has

severe recurrence for reverse effect and mutations of the target protein. Here, we report a new target protein of
RTKi, protein P, which was identified by binding proteome analysis with drug affinity responsive target stability

(DARTS) assay and liquid chromatography-Mass spectrometry (LC-MS/MS) via sequential window acquisition of all
theoretical mass spectra (SWATH) method. Direct binding of RTKi to protein P was validated by DARTS method with

dose response of RTKi and Pronase. Genetic knock down of Protein P inhibited the cell proliferation of NSCLC,
suggesting that RTKi modulates Protein P for the resistance of RTKi.