Introduction: Discoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase. Upon collagen binding, DDR1 undergoes tyrosine autophosphorylation, which consequently triggers downstream genetic and cellular pathways and plays critical roles in the regulation of cellular morphogenesis, differentiation, proliferation, adhesion, migration, and invasion. Increasing evidence suggests the potential roles of DDR1 in various human diseases including cancer, fibrosis, atherosclerosis, and other inflammatory disorders. Modulating the activity of DDR1 may be considered as a new therapeutic strategy for human cancer and inflammation-related diseases.Areas covered: This article summarizes current progress on the development of selective DDR1 inhibitors and their potential therapeutic application during the period from 2014 to 2019.Expert opinion: DDR1 is closely linked to a variety of human diseases, including fibrotic disorders, atherosclerosis, and cancer, etc. Thus, DDR1 has been considered as a new potential target for drug discovery. A number of DDR1 inhibitors has been identified in the past 5 years, but most of them display relatively broad inhibition across the kinome. New generation DDR1 inhibitors targeting the allosteric sites outside of the canonical ATP-binding pocket or extracellular domain (allosteric inhibitors) may offer a new opportunity for selective DDR1 inhibition therapy development.
Keywords: Discoidin domain receptors 1; cancer; fibrosis; inflammatory disorders; small-molecule inhibitors.