9RGC
Recombinant Human Butyrylcholinesterase in complex with LP1488 (7-[(4-{[(3,4-dimethoxybenzyl)(methyl)amino]methyl}benzyl)oxy]-4-(hydroxymethyl)-2H-chromen-2-one)
This is a non-PDB format compatible entry.
Summary for 9RGC
| Entry DOI | 10.2210/pdb9rgc/pdb |
| Descriptor | Cholinesterase, SODIUM ION, CHLORIDE ION, ... (12 entities in total) |
| Functional Keywords | butyrylcholinesterase, inhibitor, complex, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 64130.01 |
| Authors | Brazzolotto, X.,Pisani, L. (deposition date: 2025-06-06, release date: 2026-05-27, Last modification date: 2026-06-17) |
| Primary citation | Rullo, M.,La Spada, G.,Brazzolotto, X.,Marchese, S.,El Idrissi, I.G.,Miciaccia, M.,Colella, M.,Brea, J.M.,Macchia, E.,Loza, M.I.,Gottinger, A.,Scilimati, A.,Perrone, M.G.,Stefanachi, A.,Binda, C.,Leonetti, F.,Pisani, L. Leveraging multitargeting BChE-MAO B inhibitors against microglia-related neuroinflammation: in vitro biological evaluation, structure-activity relationships, drug-like properties, and X-ray crystal complexes. Eur.J.Med.Chem., 316:118961-118961, 2026 Cited by PubMed Abstract: Neuroinflammatory process is a key factor in multifaceted neurodegenerative disorders, as proved by the increased levels of pro-inflammatory mediators, primarily released by microglia and astrocytes. Following a multitarget strategy, we aimed at identifying dual inhibitors of butyrylcholinesterase (BChE) and monoamine oxidase B (MAO B). Both enzymes emerged as promising targets for tuning the inflammatory response within the central nervous system (CNS). Here we describe the synthesis, in vitro biological evaluation, and drug-likeness characterization of a series of 16 methoxy-bearing coumarin derivatives. Among them, compound 9 behaved as a well-balanced dual-acting inhibitor (hBChE, IC = 557 nM; hMAO B, IC = 142 nM) capable of mitigating interleukin-6 release from stimulated human microglia clone 3 (HMC3) cells in a dose-dependent manner and of counteracting 6-hydroxydopamine (6-OHDA) toxicity in SH-SY5Y neuroblastoma cell lines. Moreover, X-ray crystal structures of 9 in both hBChE and hMAO B were solved at 2.36 Å and 1.60 Å resolution, respectively. PubMed: 42241774DOI: 10.1016/j.ejmech.2026.118961 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.36 Å) |
Structure validation
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