Siddiqui, Kauser Kim, Geun Woong Lee, Dong Hoon Shin, Hae Ryun Yang, Eun Gyeong Lee, Nam Taek Yang, Beom-Seok 2024-01-20T22:03:39Z 2024-01-20T22:03:39Z 2021-09-03 2009-01 0918-6158 https://pubs.kist.re.kr/handle/201004/132831 Discoidin domain receptors belong to the cell surface receptor tyrosine kinase family and recognize collagens for their activating ligands. They have been implicated for cell growth and migration and their elevated expressions were observed in various human cancers. When we expressed human Discoidin domain receptor 2 (DDR2) in insect cells, the protein was targeted properly into the cell membrane and this could enforce the cells to adhere on culture plate coated with type I collagen. By taking advantage of this, we established a novel insect cell based screening protocol to identify chemicals which inhibit the interaction between DDR2 and collagen. We screened a drug-compound library to select an anti-cancer drug, actinomycin D, as the inhibitory compound. Actinomycin D prevented the activation of DDR2 by type I collagen in human embryonic kidney 293 cells with an IC50, value of 9 mu m, while it did not interfere with the activation of other receptor tyrosine kinases by their ligands. In conclusion we identified a new biological function of actinomycin D and the insect cell based method provides a useful protocol for screening inhibitors against the association of DDR2 with collagen. English PHARMACEUTICAL SOC JAPAN TYROSINE KINASES BINDING CANCER EXPRESSION CARCINOMA LINES DDR2 PROLIFERATION ACTIVATION Actinomycin D Identified as an Inhibitor of Discoidin Domain Receptor 2 Interaction with Collagen through an Insect Cell Based Screening of a Drug Compound Library Article 10.1248/bpb.32.136 1 BIOLOGICAL & PHARMACEUTICAL BULLETIN, v.32, no.1, pp.136 - 141 BIOLOGICAL & PHARMACEUTICAL BULLETIN 32 1 136 141 scie scopus 000262069200025 2-s2.0-59949089046 Pharmacology & Pharmacy Pharmacology & Pharmacy Article TYROSINE KINASES BINDING CANCER EXPRESSION CARCINOMA LINES DDR2 PROLIFERATION ACTIVATION actinomycin D discoidin domain receptor 2 collagen inhibitor screening insect cell