NIC-0102   Click here for help

GtoPdb Ligand ID: 12174

Synonyms: compound 27 [PMID: 36063115]
Compound class: Synthetic organic
Comment: NIC-0102 is a small molecule proteasome inhibitor [1]. It selectively promotes polyubiquitination and proteasome-mediated degradation of NLRP3 protein. The resulting effect is a reduction in the amount of NLRP3 available for NLRP3 inflammasome assembly. In addition, NIC-0102 appears to disrupt the NLRP3-ASC interaction which is crucial for ASC oligomerization and inflammasome complex formation. Although NIC-0102 is structurally related to bortezomib, the mechanism by which it inhibits NLRP3-dependent IL-1β secretion is different.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 4
Rotatable bonds 11
Topological polar surface area 98.66
Molecular weight 418.19
XLogP 3.75
No. Lipinski's rules broken 0
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Canonical SMILES CC(C[C@@H](B(O)O)NC(=O)[C@@H](NC(=O)c1c(F)cccc1F)Cc1ccccc1)C
Isomeric SMILES OB([C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)c1c(F)cccc1F)O
InChI InChI=1S/C21H25BF2N2O4/c1-13(2)11-18(22(29)30)26-20(27)17(12-14-7-4-3-5-8-14)25-21(28)19-15(23)9-6-10-16(19)24/h3-10,13,17-18,29-30H,11-12H2,1-2H3,(H,25,28)(H,26,27)/t17-,18-/m0/s1
Bioactivity Comments
NIC-0102 induces anti-inflammatory effects in an in vivo ulcerative colitis model [1]. It has no effects on NLRC4 or AIM2 inflammasomes. In vitro NIC-0102 inhibits activity of the 20S proteasome β5 subunit with an IC50 of 3.7 nM, and inhibits NLRP3 inflammasome-mediated IL-1β production with an IC50 of 28 nM.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
proteasome 20S subunit beta 5 Hs Inhibitor Inhibition 8.4 pIC50 - 1
pIC50 8.4 (IC50 3.7x10-9 M) [1]