7be6

Structure of DDR1 receptor tyrosine kinase in complex with inhibitor SR159

spinqualitylabelsall models 7be6, resolution 1.87Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7be6 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8708193Å Ligands: EDO, PO4, SO4, TJW Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DDR1_HUMAN Publication Abstract from PubMed Discoidin domain receptors 1 and 2 (DDR1/2) play a central role in fibrotic disorders, such as renal and pulmonary fibrosis, atherosclerosis, and various forms of cancer. Potent and selective inhibitors, so-called chemical probe compounds, have been developed to study DDR1/2 kinase signaling. However, these inhibitors showed undesired activity on other kinases such as the tyrosine protein kinase receptor TIE or tropomyosin receptor kinases, which are related to angiogenesis and neuronal toxicity. In this study, we optimized our recently published p38 mitogen-activated protein kinase inhibitor 7 toward a potent and cell-active dual DDR/p38 chemical probe and developed a structurally related negative control. The structure-guided design approach used provided insights into the P-loop folding process of p38 and how targeting of non-conserved amino acids modulates inhibitor selectivity. The developed and comprehensively characterized DDR/p38 probe, 30 (SR-302), is a valuable tool for studying the role of DDR kinase in normal physiology and in disease development. Development of a Selective Dual Discoidin Domain Receptor (DDR)/p38 Kinase Chemical Probe.,Rohm S, Berger BT, Schroder M, Chatterjee D, Mathea S, Joerger AC, Pinkas DM, Bufton JC, Tjaden A, Kovooru L, Kudolo M, Pohl C, Bullock AN, Muller S, Laufer S, Knapp S J Med Chem. 2021 Sep 23;64(18):13451-13474. doi: 10.1021/acs.jmedchem.1c00868., Epub 2021 Sep 10. PMID:34506142 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Epithelial discoidin domain-containing receptor

Proteopedia Page Contributors and Editors (what is this?)

OCA