NIC-0102
Modify Date: 2024-02-25 10:32:20
NIC-0102 structure
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Common Name | NIC-0102 | ||
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| CAS Number | 2806031-94-5 | Molecular Weight | 418.24 | |
| Density | N/A | Boiling Point | N/A | |
| Molecular Formula | C21H25BF2N2O4 | Melting Point | N/A | |
| MSDS | N/A | Flash Point | N/A | |
Use of NIC-0102NIC-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]. |
| Name | NIC-0102 |
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| Description | 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]. |
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| Related Catalog | |
| Target |
proteasom β5:3.7 nM (IC50) proteasom β2:100.5 nM (IC50) proteasom β1:113.6 nM (IC50) |
| In Vitro | 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]. Cell Viability Assay[1] Cell Line: J774A.1 and BMDM cells (LPS-primed) Concentration: 7.5, 15, 30, 60 nM Incubation Time: 1 h Result: Inhibited the release of IL-1β in a dose-dependent manner. Western Blot Analysis[1] Cell Line: J774A.1 cells (LPS-primed) Concentration: 7.5, 15, 30, 60 nM Incubation Time: 1 h Result: Dose-dependently inhibited the release of mature IL-1β and the caspase-1 p20 subunit in supernatants from J774A.1 cells but did not affect pro-IL-1β, pro-caspase-1, NLRP3, or ASC in cell lysates. Increased the polyubiquitinated NLRP3 protein in adose-dependent manner, and significantly increased the amount of c-Cbl and Cbl-b. Showed an inhibitory effect on the NF-κB subunit p65, phosphorylated p65, and NLRP3 protein at 60 nM, at which NF-κB-dependent TNF-α secretion was slightly decreased. Western Blot Analysis[1] Cell Line: J774A.1 cells (LPS-primed) Concentration: 15, 60 nM Incubation Time: 1 h Result: Inhibited the interaction between NLRP3and ASC stimulated by LPS and nigericin. Showed a concentration-dependent suppression effect on ASC oligomerization. |
| 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. 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% |
| References |
| Molecular Formula | C21H25BF2N2O4 |
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| Molecular Weight | 418.24 |