| Identification | Back Directory | [Name]
Boronic acid, B-[(1R)-1-[[(2S)-2-[(2,6-difluorobenzoyl)amino]-1-oxo-3-phenylpropyl]amino]-3-methylbutyl]- | [CAS]
2806031-94-5 | [Synonyms]
Boronic acid, B-[(1R)-1-[[(2S)-2-[(2,6-difluorobenzoyl)amino]-1-oxo-3-phenylpropyl]amino]-3-methylbutyl]- | [Molecular Formula]
C21H25BF2N2O4 | [MOL File]
2806031-94-5.mol | [Molecular Weight]
418.24 |
| Hazard Information | Back Directory | [Description]
NIC-0102 is an orally bioavailable proteasome inhibitor. NIC-0102 specifically prevents NLRP3 inflammasome activation but has no effect on NLRC4 or AIM2 inflammasomes. In vitro studies revealed that NIC-0102 induced the polyubiquitination of NLRP3, interfered with the NLRP3?ASC interaction, and blocked ASC oligomerization, thereby resulting in the inhibition of NLRP3 inflammasome activation. In addition, NIC-0102 also inhibited the production of pro-IL-1β. Importantly, NIC-0102 showed potent anti-inflammatory effects on DSS-induced ulcerative colitis model in vivo. | [Uses]
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]. | [in vivo]
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]. | Animal Model: | Male C57BL/6 mice (6 to 8-week-old; DSS-induced ulcerative colitis model)[1]. | | Dosage: | 0.125, 0.25, and 0.5 mg/kg | | Administration: | Oral gavage; single every 72 h for 10 days. | | Result: | Significantly suppressed weight and fecal occult blood.
Decreased colonic length in a dose-dependent manner.
Resulted in a dose-dependent reduction in tissue-associated IL-1β concentration and significantly inhibited pro-IL-1β.
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| Animal Model: | Male C57BL/6 mice (6 to 8-week-old)[1]. | | Dosage: | 0.5 mg/kg (for i.v.); 1 mg/kg (for p.o.) | | Administration: | Intravenous injection; Oral gavage; single. | | Result: | 1.19Pharmacokinetic Parameters of NIC-0102 in male C57BL/6 mice[1].
| IV (0.5 mg/kg) | PO (1 mg/kg) | | T1/2 (h) | 4.73 | 8.36 | | Tmax (h) | 0.08 | 0.25 | | Cmax (ng/mL) | 376.6 | 207.7 | | AUC0-∞ (h?ng/mL) | 448.8 | 489.2 | | MRT0-∞ (h) | 6.14 | - | | Vz (L/kg) | 7.7 | - | | CL (mL/min/kg) | 18.8 | - | | F (%) | - | 48.1% |
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| [IC 50]
proteasom β5: 3.7 nM (IC50); proteasom β2: 100.5 nM (IC50); proteasom β1: 113.6 nM (IC50) | [References]
[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. DOI:10.1021/acs.jmedchem.2c00523 |
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