Physicochemical Properties
| Molecular Formula | C21H25BF2N2O4 |
| Molecular Weight | 418.24 |
| Exact Mass | 418.187 |
| CAS # | 2806031-94-5 |
| PubChem CID | 164946740 |
| Appearance | White to off-white solid powder |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 30 |
| Complexity | 551 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | B([C@@H](NC(=O)[C@@H](NC(=O)C1=C(F)C=CC=C1F)CC1=CC=CC=C1)CC(C)C)(O)O |
| InChi Key | QTRFWSIBLJYXFJ-ROUUACIJSA-N |
| InChi Code | 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 |
| Chemical Name | [(1R)-1-[[(2S)-2-[(2,6-difluorobenzoyl)amino]-3-phenylpropanoyl]amino]-3-methylbutyl]boronic acid |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | In J774A.1 and BMDM cells, NIC-0102 (Compound 27) (7.5, 15, 30, 60 nM; 1h) selectively suppresses LPS-induced NLRP3 inflammasome activation [1]. Inducing NLRP3 polyubiquitination, NIC-0102 (7.5, 15, 30, 60 nM; 1h) inhibits the proteasome in LPS-primed J774A.1 cells during their activation step [1]. In LPS-primed J774A.1 cells, NIC-0102 (7.5, 15, 30, 60 nM; 1h) shows inhibitory effects on NF-κB during the priming step of the NLRP3 pathway [1]. In J774A.1 cells, LPS-induced NLRP3-ASC interaction and ASC oligomerization are blocked by NIC-0102 (15, 60 nM; 1h) [1]. |
| ln Vivo | NIC-0102 (0.125, 0.25, 0.5 mg/kg; oral administration; every 72 hours for 10 days) showed strong protective effects against DSS-induced acute colitis in mice [1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: J774A.1 and BMDM cells (LPS primed) Tested Concentrations: 7.5, 15, 30, 60 nM Incubation Duration: 1 hour Experimental Results: Inhibition of IL-1β release in a dose-dependent manner. Western Blot Analysis[1] Cell Types: J774A.1 cells (LPS primed) Tested Concentrations: 7.5, 15, 30, 60 nM Incubation Duration: 1 hour Experimental Results: Dose-dependent inhibition of release of mature IL-1β and caspase- J774A.1 The presence of 1 p20 subunit in cell supernatants did not affect pro-IL-1β, pro-caspase-1, NLRP3, or ASC in cell lysates. Increased polyubiquitinated NLRP3 protein in a dose-dependent manner and Dramatically increased the amounts of c-Cbl and Cbl-b. At 60 nM, it demonstrated an inhibitory effect on NF-κB subunit p65, phosphorylated p65 and NLRP3 protein, and NF-κB-dependent TNF-α secretion was slightly diminished at this time. Western Blot Analysis[1] Cell Types: J774A.1 cells (LPS primed) Tested Concentrations: 15, 60 nM Incubation Duration: 1 h Experimental Results: Inhibition of LPS- and nigericin-stimulated interaction b |
| Animal Protocol |
Animal/Disease Models: Male C57BL/6 mice (6 to 8 weeks old; DSS-induced ulcerative colitis model) [1]. Doses: 0.125, 0.25 and 0.5 mg/kg Route of Administration: po (oral gavage); every 72 hrs (hrs (hours)) for 10 days. Experimental Results: Significant suppression of body weight and fecal occult blood. Colon length was shortened in a dose-dependent manner. Resulting in a dose-dependent decrease in tissue-associated IL-1β concentrations and significant inhibition of pro-IL-1β. Animal/Disease Models: Male C57BL/6 mice (6 to 8 weeks old) [1]. Doses: 0.5 mg/kg (intravenous (iv) (iv)injection); 1 mg/kg (oral) Route of Administration: intravenous (iv) (iv)injection; po (oral gavage); single. Experimental Results: 1.19 pharmacokinetic/PK/PK 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 |
[1]. Discovery of a Novel Oral Proteasome Inhibitor to Block NLRP3 Inflammasome Activation with Anti-inflammation Activity. J Med Chem. 2022 Sep 5. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3910 mL | 11.9549 mL | 23.9097 mL | |
| 5 mM | 0.4782 mL | 2.3910 mL | 4.7819 mL | |
| 10 mM | 0.2391 mL | 1.1955 mL | 2.3910 mL |