The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer.

Abstract

Discoidin domain receptor (DDR) is a collagen-activated receptor tyrosine kinase that plays critical roles in regulating essential cellular processes such as morphogenesis, differentiation, proliferation, adhesion, migration, invasion, and matrix remodeling. As a result, DDR dysregulation has been attributed to a variety of human cancer disorders, for instance, non-small-cell lung carcinoma (NSCLC), ovarian cancer, glioblastoma, and breast cancer, in addition to some inflammatory and neurodegenerative disorders. Since the target identification in the early 1990s to date, a lot of efforts have been devoted to the development of DDR inhibitors. From a medicinal chemistry perspective, we attempted to reveal the progress in the development of the most promising DDR1 and DDR2 small molecule inhibitors covering their design approaches, structure-activity relationship (SAR), biological activity, and selectivity.

• Authors: Ahmed Elkamhawy, Qili Lu, Hossam Nada, Jiyu Woo, Guofeng Quan, Kyeong Lee
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 12 (Jun 18 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34207360 (Publication Type: Journal Article, Review)

Chemical References

• Biomarkers, Tumor
• Protein Kinase Inhibitors
• DDR1 protein, human
• DDR2 protein, human
• Discoidin Domain Receptor 1
• Discoidin Domain Receptor 2

Topics

• Animals
• Binding Sites
• Biomarkers, Tumor
• Discoidin Domain Receptor 1 (antagonists & inhibitors, chemistry, metabolism)
• Discoidin Domain Receptor 2 (antagonists & inhibitors, chemistry, metabolism)
• Disease Management
• Disease Susceptibility
• Drug Design
• Humans
• Inflammation (drug therapy, etiology, metabolism)
• Molecular Docking Simulation
• Molecular Dynamics Simulation
• Molecular Structure
• Molecular Targeted Therapy
• Neoplasms (drug therapy, etiology, metabolism, pathology)
• Neurodegenerative Diseases (drug therapy, etiology, metabolism)
• Protein Binding
• Protein Conformation
• Protein Kinase Inhibitors (chemistry, pharmacology, therapeutic use)
• Structure-Activity Relationship