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Small Molecule Inhibitors of Discoidin Domain Receptors (DDRs)

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Discoidin Domain Receptors in Health and Disease

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Abstract

The discoidin domain receptors (DDRs) play crucial roles in the regulation of fundamental cellular processes, such as proliferation, survival, differentiation, adhesion, and matrix remodeling. Dysregulation of DDRs has been linked to many human diseases, including fibrotic disorders, atherosclerosis, and cancer. Thus, DDRs have been considered as emerging potential molecular targets for new drug discovery. Several classes of DDR small molecular inhibitors have been discovered in recent years. This chapter will provide an updated overview on the chemical structures, mechanism of action (MOA), and potential medical implications of the newly identified DDR small molecule inhibitors.

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Abbreviations

DDRs:

Discoidin domain receptors

2D:

Two dimensional

DS:

Discoidin domain

ECM:

Extracellular matrix

EJXM:

Extracellular juxtamembrane

FDA:

Food and Drug Administration

FLiK:

Fluorescent labels in kinases

FUSION:

Functional Signature-Based Ontology

IJXM:

Intracellular juxtamembrane

IR:

Insulin receptor

KD:

Kinase domain

MOA:

Mechanism of action

NMR:

Nuclear magnetic resonance

NSCLC:

Non-small cell lung cancer

PK:

Pharmacokinetics

PMBCl:

para-Methoxybenzyl chloride

QSAR:

Quantitative structure-activity relationship

RTKs:

Receptor tyrosine kinases

SQCC:

Squamous lung cancer

S768R:

Serine 768 to arginine 768

TMT:

Transmembrane

VEGFR:

Vascular endothelial growth factor receptor

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Authors and Affiliations

  1. School of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou, 510632, China

    Xiaoyun Lu & Ke Ding

  2. Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, #190 Kaiyuan Avenue, Guangzhou, 510530, China

    Xiaoyun Lu & Ke Ding

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  1. Xiaoyun Lu
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Correspondence to Ke Ding .

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Editors and Affiliations

  1. Department of Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA

    Rafael Fridman

  2. Division of Cancer Biology, The Institute of Cancer Research, London, United Kingdom

    Paul H. Huang

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Lu, X., Ding, K. (2016). Small Molecule Inhibitors of Discoidin Domain Receptors (DDRs). In: Fridman, R., Huang, P. (eds) Discoidin Domain Receptors in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-6383-6_10

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