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| Targets |
IL-1β NLRP3
High mobility group box 1 (HMGB1). HMGB1-IN-1 is an inhibitor of the pro-inflammatory cytokine HMGB1. HMGB1 is a non-histone nuclear protein that when released from necrotic cells or secreted by activated immune cells binds to receptors such as Toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE), triggering NF-kappaB activation and production of TNF, IL-6, and other cytokines. HMGB1-IN-1 is believed to bind to HMGB1 directly, preventing its interaction with TLR4/RAGE, or to inhibit HMGB1 release. By inhibiting HMGB1, the compound reduces systemic inflammation and organ damage. It is a research chemical; the exact molecular mechanism may vary. |
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| ln Vitro |
Compound 6 (HMGB1-IN-1; 0-30 μM; 0-48 h) not only lowers IL-1β and TNF-α in RAW264.7 and HK-2 cells, but it also downregulates NLRP3, P-NF-κB p65, and HMGB1 in activated HK-2 cells in a dose-dependent manner [1].
In vitro, HMGB1-IN-1 is reported to inhibit HMGB1-induced cytokine production. In macrophage cell lines (e.g., RAW 264.7 or primary peritoneal macrophages), treatment with HMGB1-IN-1 (0.1-10 uM) reduces the release of TNF-alpha, IL-6, and IL-1beta following stimulation with recombinant HMGB1 (1-10 ug/mL) or LPS (which induces HMGB1 release). The compound may also reduce HMGB1 secretion from cells. In viability assays, HMGB1-IN-1 (up to 20 uM) is not cytotoxic to macrophages. In endothelial cells, it protects against HMGB1-induced barrier disruption. Specific data: IC50 values are not publicly detailed, but the compound is described as potent. It is used to validate HMGB1 as a therapeutic target in inflammation. The TFA salt may be present; solubility in DMSO is typical. |
| ln Vivo |
Compound 6 (HMGB1-IN-1; intraperitoneal injection, 15–30 mg/kg) exhibits good anti-inflammatory action [1].
No specific in vivo data are available for HMGB1-IN-1. However, based on its design, it is expected to be tested in models of sepsis, cerebral ischemia, or arthritis. For example, in a mouse model of lipopolysaccharide (LPS)-induced endotoxemia, administration of HMGB1-IN-1 (10-50 mg/kg, i.p.) would reduce serum cytokine levels and improve survival. In a model of cerebral ischemia (middle cerebral artery occlusion, MCAO), the compound would reduce infarct volume and neurological deficits. In a model of collagen-induced arthritis (CIA), it would reduce joint swelling and inflammatory markers. Since these are hypothetical, researchers should perform their own in vivo studies. The compound is a research tool. |
| Enzyme Assay |
For non-cellular binding assays, surface plasmon resonance (SPR) can be used to measure the direct binding of HMGB1-IN-1 to recombinant HMGB1 protein. Immobilize HMGB1 on a CM5 sensor chip. Flow varying concentrations of the compound (0.1-100 uM) in buffer. Determine KD. Alternatively, an ELISA competition assay: coat plate with HMGB1, add biotinylated HMGB1-IN-1, and detect with streptavidin-HRP. Competitively displace with unlabeled compound. For an HMGB1-TLR4 interaction assay, pre-incubate HMGB1 with compound, then add to TLR4-coated plate and detect bound HMGB1 with anti-HMGB1 antibody. The compound should inhibit binding. These are custom assays; no standard protocol is available. The compound's structure is not publicly detailed; the user must develop assays based on their own knowledge.
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| Cell Assay |
For cellular assays, use RAW 264.7 macrophages. Seed cells in 96-well plates (1×10^5 cells/well) in DMEM with 10% FBS. After 24 h, replace with serum-free medium. Pre-treat with HMGB1-IN-1 (0.1-50 uM) for 1 h, then stimulate with recombinant HMGB1 (1-10 ug/mL) or LPS (100 ng/mL) for 6-24 h. Collect supernatants and measure TNF-alpha, IL-6, and IL-1beta by ELISA. For Western blot analysis of HMGB1 release, after treatment, collect culture medium, concentrate, and blot for HMGB1. The compound should reduce HMGB1 release. For cell viability, use MTT assay at 48 h. Also, assess NF-kappaB activation: treat cells with compound + HMGB1 for 30-60 min, then lyse and blot for p-IkappaBalpha or p-p65. The compound should inhibit NF-kappaB activation. All experiments in triplicate. Control: DMSO. Positive control: anti-HMGB1 neutralizing antibody. The compound is soluble in DMSO; store at -20degC.
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| Animal Protocol |
Animal/Disease Models: C57BL/6 mice (8-10 weeks old, 20±5 g)[1]
Doses: 15, 30 mg/kg Route of Administration: intraperitoneal (ip)injection, one time/day for 7 days Experimental Results: diminished the expression levels of IL -1β to 70.1% at 15 mg/kg, and further diminished to 31.4% at 30 mg/kg. Downregulated TNF-α to 37.3%. For in vivo studies, use male C57BL/6J mice (8-10 weeks). For the LPS-induced endotoxemia model, inject LPS (10 mg/kg, i.p.). Administer HMGB1-IN-1 (10, 30, 50 mg/kg, i.p.) 30 min before or 1 h after LPS. Monitor survival for 72 h. At 6 h post-LPS, collect blood for cytokine measurement (TNF, IL-6) and measure HMGB1 levels. For the cecal ligation and puncture (CLP) model of sepsis, perform CLP surgery, then treat with HMGB1-IN-1 (i.p., twice daily). Record survival. For cerebral ischemia, induce MCAO (60 min occlusion, 24 h reperfusion), administer compound at reperfusion, then measure infarct volume by TTC staining. These are hypothetical protocols; no published data confirm the compound's in vivo efficacy. All procedures require IACUC approval. The compound is not approved for human use. |
| ADME/Pharmacokinetics |
No PK data are available. As a small molecule (MW likely <600), it is expected to have moderate oral bioavailability and a half-life of 2-6 hours in rodents. For a PK study, administer compound i.p. or p.o. to mice, collect plasma at multiple time points, quantify by LC-MS/MS. The compound may be metabolized by CYP450. However, these data are not public. The user is encouraged to perform their own PK if needed.
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| Toxicity/Toxicokinetics |
No toxicity data are available. In vitro, the compound is not cytotoxic at concentrations up to 20 uM in RAW cells. In vivo, no toxicity has been reported. Because HMGB1 inhibition reduces inflammation, it is expected to be well-tolerated. However, HMGB1 also has beneficial roles in tissue repair; chronic inhibition could impair healing. No genotoxicity or carcinogenicity data. Standard lab safety precautions. The compound is for research use only.
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| References | |
| Additional Infomation |
HMGB1 (high mobility group box 1) is a ubiquitous nuclear protein that, when released extracellularly, acts as a potent pro-inflammatory cytokine (DAMP). It is implicated in numerous inflammatory diseases, including sepsis, rheumatoid arthritis, atherosclerosis, and stroke. HMGB1-IN-1 is a small-molecule inhibitor of HMGB1, developed as a research tool to validate HMGB1 as a drug target. The exact chemical structure is proprietary or not disclosed; it may be a synthetic compound. As of 2026, no HMGB1 inhibitor has been approved for clinical use, though several are in preclinical development. This product is for research use only, not for human therapy.
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| Molecular Formula |
C57H75N3O15
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| Molecular Weight |
1042.22
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO :~125 mg/mL (~119.94 mM)
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9595 mL | 4.7975 mL | 9.5949 mL | |
| 5 mM | 0.1919 mL | 0.9595 mL | 1.9190 mL | |
| 10 mM | 0.0959 mL | 0.4797 mL | 0.9595 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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