6hp9
Structure of the kinase domain of human DDR1 in complex with a 2-Amino-2,3-Dihydro-1H-Indene-5-Carboxamide-based inhibitorStructure of the kinase domain of human DDR1 in complex with a 2-Amino-2,3-Dihydro-1H-Indene-5-Carboxamide-based inhibitor
Structural highlights
FunctionPublication Abstract from PubMedPancreatic cancer is a leading cause of cancer-related death. A series of 2-amino-2, 3-dihydro-1H-indene-5-carboxamide derivatives were designed and synthesized as novel selective DDR1 inhibitors to exhibit promising in vitro and in vivo anti-pancreatic cancer activity. One of the representative compounds, 7f, binds with DDR1 with a Kd value of 5.9 nM and suppresses the kinase activity with an IC50 value of 14.9 nM, but is significantly less potent for majority of a panel of 403 wild-type kinases. The compound potently inhibited collagen-induced epithelial-mesenchymal transition (EMT) and dose-dependently suppressed colony formation of pancreatic cancer cells. Furthermore, 7f also demonstrated reasonable pharmacokinetic profiles and displayed promising in vivo therapeutic efficacy in an orthotopic mouse model of pancreatic cancer. Compound 7f may serve as a new lead compound for future drug discovery. 2-Amino-2, 3-Dihydro-1H-Indene-5-Carboxamide-Based Discoidin Domain Receptors 1 (DDR1) Inhibitors: Design, Synthesis, and In Vivo Anti-pancreatic Cancer Efficacy.,Zhu D, Huang H, Pinkas D, Luo J, Ganguly D, Fox AE, Arner E, Xiang Q, Tu ZC, Bullock AN, Brekken RA, Ding K, Lu X J Med Chem. 2019 Jul 16. doi: 10.1021/acs.jmedchem.9b00365. PMID:31310125[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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