Quantitative Proteomics Reveals Cellular Off-Targets of a DDR1 Inhibitor

Jiaqian Xu; Zhang Zhang; Ligen Lin; Hongyan Sun; Lorenzo V. White; Ke Ding; Zhengqiu Li

doi:10.1021/acsmedchemlett.9b00658

Quantitative Proteomics Reveals Cellular Off-Targets of a DDR1 Inhibitor

Jiaqian Xu
, Zhang Zhang
, Ligen Lin
, Hongyan Sun
, Lorenzo V. White
, Ke Ding^*
, Zhengqiu Li^*

^*Corresponding author for this work

Department of Chemistry

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

12 Citations (Scopus)

Abstract

Target identification of small molecules is a great challenge but an essential step in drug discovery. Here, a quantitative proteomics approach has been used to characterize the cellular targets of DR, a DDR1 inhibitor. By taking advantage of competitive affinity-based protein profiling coupled with bioimaging, Cathepsin D (CTSD) was found to be the principle off-target of DR in human cancer cells. Further findings suggest the potential of DR as a novel CTSD inhibitor for breast cancer treatment. In addition, a trans-cyclooctene (TCO) containing probe was developed to track the binding between DR and its target proteins in living systems and could be a useful tool for DDR1 detection.

Original language	English
Pages (from-to)	535-540
Journal	ACS Medicinal Chemistry Letters
Volume	11
Issue number	4
Online published	5 Feb 2020
DOIs	https://doi.org/10.1021/acsmedchemlett.9b00658
Publication status	Published - 9 Apr 2020

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Keywords

bioimaging
chemoproteomics
DDR1
photoaffinity labeling
target identification

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10.1021/acsmedchemlett.9b00658

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title = "Quantitative Proteomics Reveals Cellular Off-Targets of a DDR1 Inhibitor",

abstract = "Target identification of small molecules is a great challenge but an essential step in drug discovery. Here, a quantitative proteomics approach has been used to characterize the cellular targets of DR, a DDR1 inhibitor. By taking advantage of competitive affinity-based protein profiling coupled with bioimaging, Cathepsin D (CTSD) was found to be the principle off-target of DR in human cancer cells. Further findings suggest the potential of DR as a novel CTSD inhibitor for breast cancer treatment. In addition, a trans-cyclooctene (TCO) containing probe was developed to track the binding between DR and its target proteins in living systems and could be a useful tool for DDR1 detection.",

keywords = "bioimaging, chemoproteomics, DDR1, photoaffinity labeling, target identification",

author = "Jiaqian Xu and Zhang Zhang and Ligen Lin and Hongyan Sun and White, \{Lorenzo V.\} and Ke Ding and Zhengqiu Li",

year = "2020",

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doi = "10.1021/acsmedchemlett.9b00658",

language = "English",

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journal = "ACS Medicinal Chemistry Letters",

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T1 - Quantitative Proteomics Reveals Cellular Off-Targets of a DDR1 Inhibitor

AU - Xu, Jiaqian

AU - Zhang, Zhang

AU - Lin, Ligen

AU - Sun, Hongyan

AU - White, Lorenzo V.

AU - Ding, Ke

AU - Li, Zhengqiu

PY - 2020/4/9

Y1 - 2020/4/9

N2 - Target identification of small molecules is a great challenge but an essential step in drug discovery. Here, a quantitative proteomics approach has been used to characterize the cellular targets of DR, a DDR1 inhibitor. By taking advantage of competitive affinity-based protein profiling coupled with bioimaging, Cathepsin D (CTSD) was found to be the principle off-target of DR in human cancer cells. Further findings suggest the potential of DR as a novel CTSD inhibitor for breast cancer treatment. In addition, a trans-cyclooctene (TCO) containing probe was developed to track the binding between DR and its target proteins in living systems and could be a useful tool for DDR1 detection.

AB - Target identification of small molecules is a great challenge but an essential step in drug discovery. Here, a quantitative proteomics approach has been used to characterize the cellular targets of DR, a DDR1 inhibitor. By taking advantage of competitive affinity-based protein profiling coupled with bioimaging, Cathepsin D (CTSD) was found to be the principle off-target of DR in human cancer cells. Further findings suggest the potential of DR as a novel CTSD inhibitor for breast cancer treatment. In addition, a trans-cyclooctene (TCO) containing probe was developed to track the binding between DR and its target proteins in living systems and could be a useful tool for DDR1 detection.

KW - bioimaging

KW - chemoproteomics

KW - DDR1

KW - photoaffinity labeling

KW - target identification

UR - https://www.scopus.com/pages/publications/85080126008#tab=impact

UR - https://www.scopus.com/pages/publications/85080126008

U2 - 10.1021/acsmedchemlett.9b00658

DO - 10.1021/acsmedchemlett.9b00658

M3 - RGC 21 - Publication in refereed journal

C2 - 32292561

SN - 1948-5875

VL - 11

SP - 535

EP - 540

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 4

ER -

Quantitative Proteomics Reveals Cellular Off-Targets of a DDR1 Inhibitor

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