Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/ijms22126535
Keywords
discoidin domain receptor (DDR); cancer; kinase inhibitors; structure-activity relationship (SAR); DDR1 and DDR2
Funding
- national Research Foundation of Korea (NRF) - Korea government (MSIT) [NRF-2018R1A5A2023127]
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DDR is a crucial collagen-activated receptor tyrosine kinase that regulates essential cellular processes, and its dysregulation is associated with various cancers and diseases. Efforts have been made in the development of DDR inhibitors, focusing on the progress of DDR1 and DDR2 inhibitors.
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.
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