NIC-0102

• CAT Number: I042864
• CAS Number: 2806031-94-5
• Molecular Formula: C21H25BF2N2O4
• Molecular Weight: 418.24
• Purity: ≥95%
• Synonyms: [(1R)-1-[[(2S)-2-[(2,6-difluorobenzoyl)amino]-3-phenylpropanoyl]amino]-3-methylbutyl]boronic acid
• 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
• InChIKey: QTRFWSIBLJYXFJ-ROUUACIJSA-N
• SMILES: B(C(CC(C)C)NC(=O)C(CC1=CC=CC=C1)NC(=O)C2=C(C=CC=C2F)F)(O)O

NIC-0102 is an orally active proteasome inhibitor (pIC50=7.55) that specifically inhibits NLRP3 inflammatory vesicle activation. NIC-0102 shows potent anti-inflammatory effects in a model of dextran sulfate sodium (DSS)-induced ulcerative colitis. NIC-0102 also inhibits production of pro-IL-1β[1].
NIC-0102 (compound 27) (7.5, 15, 30, 60 nM; 1h) specifically suppresses NLRP3 inflammasome activation in LPS-primed J774A.1 and BMDM cells[1].
NIC-0102 (7.5, 15, 30, 60 nM; 1h) induces polyubiquitination of NLRP3 via inhibition of the proteasome during the activation step in LPS-primed J774A.1 cells[1].
NIC-0102 (7.5, 15, 30, 60 nM; 1h) exhibits inhibitory effects on NF-κB in the priming step of the NLRP3 pathway in LPS-primed J774A.1 cells[1].
NIC-0102 (15, 60 nM; 1h) blocks NLRP3-ASC interaction and ASC oligomerization in LPS-primed J774A.1 cells[1].
NIC-0102 (0.125, 0.25, 0.5 mg/kg; p.o.; single every 72 h for 10 days) shows strong protection against DSS-induced acute colitis in mice[1].

Reference

[1]. Wu X, et al. Discovery of a Novel Oral Proteasome Inhibitor to Block NLRP3 Inflammasome Activation with Anti-inflammation Activity. J Med Chem. 2022 Sep 5.
 [Content Brief]