NU6300 |
Catalog No.GC32829
One-Click Copy Product Info
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NU6300 is a small molecule compound that specifically inhibits pyroptosis by covalently binding to the C191 site of the Gasdermin D (GSDMD) protein.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2070015-09-5
Sample solution is provided at 25 µL, 10mM.
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NU6300 is a small molecule compound that specifically inhibits pyroptosis by covalently binding to the C191 site of the Gasdermin D (GSDMD) protein[1]. NU6300 can covalently react with the cysteine 191 (C191) of GSDMD, a key executioner protein in pyroptosis, thereby blocking the cleavage and palmitoylation of GSDMD. This prevents the N-terminal fragment of GSDMD from forming pores in the cell membrane, ultimately inhibiting the occurrence of pyroptosis[2].
In vitro, pretreatment of human monocytic THP-1 cells, mouse bone marrow-derived macrophages, and HEK-293T cells with NU6300 (0.5–10μM) for 40 minutes to 16 hours, followed by activation of AIM2, NLRC4, or NLRP3 inflammasomes via nigericin (10μM; 1h), poly(dA:dT) (1μg/mL; 6h), or flagellin (1μg/mL; 6h), significantly inhibited the cleavage and palmitoylation of GSDMD. This blocked its membrane localization and oligomerization, thereby reducing pyroptosis and the release of the proinflammatory cytokine IL-1β[3].
In vivo, NU6300 (5mg/kg) was administered via intraperitoneal injection in DSS-induced colitis mouse models (daily for five consecutive days) or LPS-induced sepsis mouse models (single injection). NU6300 significantly alleviated body weight loss, disease activity index elevation, colon shortening, and histopathological damage in DSS-induced colitis mice, while also improving epithelial and mucosal damage, crypt dilation, and goblet cell depletion. Additionally, NU6300 significantly increased the survival rate of septic mice, reduced the spleen index, and lowered the levels of proinflammatory cytokines[3].
References:
[1] Shua Y, Wang Q, Wang Y, et al. Progress in small-molecule inhibitors of gasdermin D. Eur J Med Chem. 2025 Dec 15;300:118171.
[2] Anscombe E, Meschini E, Mora-Vidal R, et al. Identification and Characterization of an Irreversible Inhibitor of CDK2. Chem Biol. 2015 Sep 17;22(9):1159-64.
[3] Jiang X, Zhang X, Cai X, et al. NU6300 covalently reacts with cysteine-191 of gasdermin D to block its cleavage and palmitoylation. Sci Adv. 2024 Feb 9;10(6):eadi9284.
| Cell experiment [1]: | |
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Cell lines |
THP-1 cells (human monocytic cell line), mouse bone marrow-derived macrophages (BMDMs), HEK-293T cells (human embryonic kidney cell line) |
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Preparation Method |
THP-1 cells were maintained in RPMI 1640 medium supplemented with 10% FBS and 1% penicillin/streptomycin. BMDMs were differentiated from bone marrow cells in DMEM supplemented with 10% FBS and 20% L929-conditioned medium. HEK-293T cells were maintained in DMEM supplemented with 10% FBS. Cells were pretreated with NU6300 (0.5-10μM) for 40 minutes to 16 hours, followed by Nigericin (10μM; 1h), Poly(dA:dT) (1μg/mL; 6h), or Flagellin (1μg/mL; 6h) stimulation. |
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Reaction Conditions |
0.5-10μM; 40min-16h pretreatment |
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Applications |
NU6300 significantly inhibited GSDMD cleavage and palmitoylation, blocked GSDMD membrane localization and oligomerization, and reduced pyroptosis and IL-1β release in AIM2, NLRC4, and NLRP3 inflammasome-activated cells. NU6300 also feedback inhibited ASC oligomerization and caspase-1 activation under NLRP3 inflammasome activation conditions. |
| Animal experiment [1]: | |
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Animal models |
C57BL/6J mice, BALB/c mice |
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Preparation Method |
For the colitis model, male C57BL/6J mice were administered 3.25% dextran sulfate sodium (DSS) in drinking water for 6 days, followed by normal water. NU6300 (5, 10, 20mg/kg) or Necrosulfonamide (NSA, 20mg/kg) was intraperitoneally administered daily for 5 consecutive days concurrently with the return to normal water. For the sepsis model, mice were intraperitoneally administered NU6300 (5, 10mg/kg) or NSA (10mg/kg) 1 hour before LPS (8mg/kg for BALB/c, 50mg/kg for C57BL/6J) injection. |
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Dosage form |
5-20mg/kg; i.p.; Daily administration for 5 days (colitis) or single injection (sepsis). |
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Applications |
NU6300 administration significantly attenuated body weight loss, disease activity index, colon shortening, and pathological damage (epithelial/mucosal damage, crypt dilation, goblet cell depletion) in DSS-induced colitis. |
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References: |
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| Cas No. | 2070015-09-5 | SDF | |
| Canonical SMILES | O=S(C(C=C1)=CC=C1NC2=NC(OCC3CCCCC3)=C4C(NC=N4)=N2)(C=C)=O | ||
| Formula | C20H23N5O3S | M.Wt | 413.49 |
| Solubility | DMSO : ≥ 32 mg/mL (77.39 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4184 mL | 12.0922 mL | 24.1844 mL |
| 5 mM | 483.7 μL | 2.4184 mL | 4.8369 mL |
| 10 mM | 241.8 μL | 1.2092 mL | 2.4184 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 22 reference(s) in Google Scholar.)