7MFH
Crystal structure of BIO-32546 bound mouse Autotaxin
Summary for 7MFH
| Entry DOI | 10.2210/pdb7mfh/pdb |
| Descriptor | Ectonucleotide 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 Keywords | hydrolase inhibitor, autotaxin, hydrolase, hydrolase-inhibitor complex, hydrolase/inhibitor |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 99445.25 |
| Authors | Chodaparambil, J.V. (deposition date: 2021-04-09, release date: 2022-04-13, Last modification date: 2023-10-18) |
| Primary citation | Ma, 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: 34267882DOI: 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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