6HP9

Structure of the kinase domain of human DDR1 in complex with a 2-Amino-2,3-Dihydro-1H-Indene-5-Carboxamide-based inhibitor

Summary for 6HP9

• Entry DOI: 10.2210/pdb6hp9/pdb
• Descriptor: Epithelial discoidin domain-containing receptor 1, (2~{R})-~{N}-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-2-(pyrimidin-5-ylamino)-2,3-dihydro-1~{H}-indene-5-carboxamide (3 entities in total)
• Functional Keywords: ddr1, structural genomics, structural genomics consortium, sgc, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 72465.13

Authors

Pinkas, D.M.,Fox, A.E.,Kupinska, K.,Burgess-Brown, N.A.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Bullock, A.N.,Structural Genomics Consortium (SGC) (deposition date: 2018-09-19, release date: 2019-01-30, Last modification date: 2024-01-24)

Primary citation

Zhu, D.,Huang, H.,Pinkas, D.M.,Luo, J.,Ganguly, D.,Fox, A.E.,Arner, E.,Xiang, Q.,Tu, Z.C.,Bullock, A.N.,Brekken, R.A.,Ding, K.,Lu, X.
2-Amino-2,3-dihydro-1H-indene-5-carboxamide-Based Discoidin Domain Receptor 1 (DDR1) Inhibitors: Design, Synthesis, and in Vivo Antipancreatic Cancer Efficacy.
J.Med.Chem., 62:7431-7444, 2019

PubMed Abstract: A series of 2-amino-2,3-dihydro-1-indene-5-carboxamides were designed and synthesized as new selective discoidin domain receptor 1 (DDR1) inhibitors. One of the representative compounds, , bound with DDR1 with a value of 5.9 nM and suppressed the kinase activity with an half-maximal (50%) inhibitory concentration value of 14.9 nM. potently inhibited collagen-induced DDR1 signaling and epithelial-mesenchymal transition, dose-dependently suppressed colony formation of pancreatic cancer cells, and exhibited promising in vivo therapeutic efficacy in orthotopic mouse models of pancreatic cancer.

PubMed: 31310125
DOI: 10.1021/acs.jmedchem.9b00365

Experimental method

X-RAY DIFFRACTION (1.96 Å)