7p0k

Crystal structure of Autotaxin (ENPP2) with 18F-labeled positron emission tomography ligand

spinqualitylabelsall models 7p0k, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7p0k is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: 4I0, BMA, CA, IOD, MAN, NAG, SCN, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ENPP2_RAT Publication Abstract from PubMed Autotaxin (ATX) is a secreted phosphodiesterase that has been implicated in a remarkably wide array of pathologies, especially in fibrosis and cancer. While ATX inhibitors have entered the clinical arena, a validated probe for positron emission tomography (PET) is currently lacking. With the aim to develop a suitable ATX-targeted PET radioligand, we have synthesized a focused library of fluorinated imidazo[1,2-a]pyridine derivatives, determined their inhibition constants, and confirmed their binding mode by crystallographic analysis. Based on their promising in vitro properties, compounds 9c, 9f, 9h, and 9j were radiofluorinated. Also, a deuterated analog of [(18)F]9j, designated as [(18)F]ATX-1905 ([(18)F]20), was designed and proved to be highly stable against in vivo radiodefluorination compared with [(18)F]9c, [(18)F]9f, [(18)F]9h, and [(18)F]9j. These results along with in vitro and in vivo studies toward ATX in a mouse model of LPS-induced liver injury suggest that [(18)F]ATX-1905 is a suitable PET probe for the non-invasive quantification of ATX. Imaging Autotaxin In Vivo with (18)F-Labeled Positron Emission Tomography Ligands.,Deng X, Salgado-Polo F, Shao T, Xiao Z, Van R, Chen J, Rong J, Haider A, Shao Y, Josephson L, Perrakis A, Liang SH J Med Chem. 2021 Oct 28;64(20):15053-15068. doi: 10.1021/acs.jmedchem.1c00913. , Epub 2021 Oct 18. PMID:34662125 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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