GDC-2394   Click here for help

GtoPdb Ligand ID: 12280

Synonyms: compound 20 [PMID: 36279149] | GDC2394
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: GDC-2394 is a potent NLRP3 inhibitor [1]. It binds to an allosteric pocket in NLRP3's NACHT domain. GDC-2394 inhibits activated NLRP3 inflammasome-mediated production of IL-1β and IL-18 in vitro (IC50s 16 nM and 17 nM respectively, in human monocyte-derived macrophages), and orally administered GDC-2394 reduces inflammation in animal models.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 3
Rotatable bonds 6
Topological polar surface area 122.73
Molecular weight 431.16
XLogP 3.06
No. Lipinski's rules broken 0
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Canonical SMILES CN[C@@H]1COc2n(C1)ncc2S(=O)(=O)NC(=O)Nc1c2CCCc2cc2c1CCC2
Isomeric SMILES C1CCc2c(c3CCCc3cc12)NC(=O)NS(=O)(=O)c1cnn2c1OC[C@H](C2)NC
InChI InChI=1S/C20H25N5O4S/c1-21-14-10-25-19(29-11-14)17(9-22-25)30(27,28)24-20(26)23-18-15-6-2-4-12(15)8-13-5-3-7-16(13)18/h8-9,14,21H,2-7,10-11H2,1H3,(H2,23,24,26)/t14-/m0/s1
1. McBride C, Trzoss L, Povero D, Lazic M, Ambrus-Aikelin G, Santini A, Pranadinata R, Bain G, Stansfield R, Stafford JA et al.. (2022)
Overcoming Preclinical Safety Obstacles to Discover (S)-N-((1,2,3,5,6,7-Hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonamide (GDC-2394): A Potent and Selective NLRP3 Inhibitor.
J Med Chem, 65 (21): 14721-14739. [PMID:36279149]