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7MFH

Crystal structure of BIO-32546 bound mouse Autotaxin

Summary for 7MFH
Entry DOI10.2210/pdb7mfh/pdb
DescriptorEctonucleotide pyrophosphatase/phosphodiesterase family member 2, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
Functional Keywordshydrolase inhibitor, autotaxin, hydrolase, hydrolase-inhibitor complex, hydrolase/inhibitor
Biological sourceMus musculus (Mouse)
Total number of polymer chains1
Total formula weight99445.25
Authors
Chodaparambil, J.V. (deposition date: 2021-04-09, release date: 2022-04-13, Last modification date: 2024-11-20)
Primary citationMa, B.,Zhang, L.,Sun, L.,Xin, Z.,Kumaravel, G.,Marcotte, D.,Chodaparambil, J.V.,Wang, Q.,Wehr, A.,Jing, J.,Hong, V.S.,Wang, T.,Huang, C.,Shao, Z.,Mi, S.
Discovery of Potent Selective Nonzinc Binding Autotaxin Inhibitor BIO-32546.
Acs Med.Chem.Lett., 12:1124-1129, 2021
Cited by
PubMed Abstract: Autotaxin (ATX) is a lysophospholipase D that is the main enzyme responsible for generating LPA in body fluids. Although ATX was isolated from a conditioned medium of melanoma cells, later it was discovered to play a critical role in vascular and neuronal development. ATX has also been implicated in primary brain tumor, fibrosis, and rheumatoid arthritis, as well as neurological diseases such as multiple sclerosis, Alzheimer's disease, and neuropathic pain. As ATX and LPA levels are increased upon neuronal injury, a selective ATX inhibitor could provide a new approach to treat neuropathic pain. Herein we describe the discovery of a novel series of nonzinc binding reversible ATX inhibitors, particularly a potent, selective, orally bioavailable, brain-penetrable tool compound BIO-32546, as well as its synthesis, X-ray cocrystal structure, pharmacokinetics, and in vivo efficacy.
PubMed: 34267882
DOI: 10.1021/acsmedchemlett.1c00211
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.3 Å)
Structure validation

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