NP3-253   Click here for help

GtoPdb Ligand ID: 13645

Synonyms: compound 16 [PMID: 39574318] | NP3253
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: NP3-253 is a brain-penetrant tricyclic NLRP3 inhibitor [2]. The compound acts to lock the receptor's NACHT domain in a closed and inactive conformation, thus blocking inflammasome activation. NP3-253 is proposed to suppress inflammasome-mediated pro-inflammatory cytokine production in diseases that are associated with chronic peripheral and neuroinflammation (cardiometabolic diseases, Alzheimer's disease, Parkinson's disease, multiple sclerosis) [1].
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 60.22
Molecular weight 380.41
XLogP 3.84
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES CCN1CCC[C@H](C1)NC2=CC=C(C3=C(C=C(C=C3C)C(F)(F)F)O)N=N2
Isomeric SMILES CCN1CCC[C@H](C1)NC2=CC=C(N=N2)C3=C(O)C=C(C=C3C)C(F)(F)F
InChI InChI=1S/C19H23F3N4O/c1-3-26-8-4-5-14(11-26)23-17-7-6-15(24-25-17)18-12(2)9-13(10-16(18)27)19(20,21)22/h6-7,9-10,14,27H,3-5,8,11H2,1-2H3,(H,23,25)/t14-/m1/s1
InChI Key UVVZGYXCKGWWCC-CQSZACIVSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Harrison D. (2024)
Brain Penetrant NLRP3 Inhibitors: The Discovery of a Panacea?.
J Med Chem, 67 (23): 20776-20779. [PMID:39621542]
2. Mackay A, Velcicky J, Gommermann N, Mattes H, Janser P, Wright M, Dubois C, Brenneisen S, Ilic S, Vangrevelinghe E et al.. (2024)
Discovery of NP3-253, a Potent Brain Penetrant Inhibitor of the NLRP3 Inflammasome.
J Med Chem, 67 (23): 20780-20798. [PMID:39574318]