| Size | Price | Stock | Qty |
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| Targets |
LMT-28 targets the interleukin-6 (IL-6) signaling pathway by directly binding to gp130, a shared signal-transducing receptor subunit for the IL-6 cytokine family. IL-6 is a pleiotropic cytokine that plays a central role in inflammation, immune responses, and bone metabolism. The IL-6 signal is transduced through a receptor complex composed of IL-6Rα and gp130, leading to the activation of the JAK2/STAT3 signaling pathway. LMT-28 functions as a direct inhibitor of this protein-protein interaction by binding to gp130. This binding selectively inhibits IL-6-induced phosphorylation of STAT3, JAK2, and gp130, thereby blocking downstream signaling.
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| ln Vitro |
At 50 μM, LMT-28 has an IC50 value of 5.9 μM and can inhibit IL-6-induced luciferase activity by almost 90%. LMT-28 (1–100 μM; 1 hour) specifically inhibits IL-6-induced STAT3, JAK2, and gp130 [1]. Cell erythroid cell line TF-1 phosphorylation is inhibited by LMT-28 (1–100 μM; 72 hours) in relation to IL-6-induced phosphorylation of human tissue.
In vitro, LMT-28 is a potent and selective inhibitor of IL-6 signaling. It inhibits IL-6-induced phosphorylation of STAT3, JAK2, and gp130. The compound shows low toxicity in vitro. It selectively targets the IL-6 pathway without affecting other cytokine signaling pathways. Detailed IC50 values for inhibition of STAT3 phosphorylation are not extensively reported, but the compound's activity is confirmed through functional assays measuring downstream effects of IL-6 stimulation. |
| ln Vivo |
CIA is attenuated by LMT-28 (0-0.5 mg/kg; applied topically once daily for 15 days)[1]. LMT-28 simulates the development of face inflammation (0.25 or 1 mg/kg; po). By directly binding to gp130, the -28 bridge inhibits gp130's reaction to the IL-6/IL-6Rα combination [1].
In vivo, LMT-28 has demonstrated efficacy in various disease models. In diabetic models, LMT-28 reduces LPS-induced bone resorption around implants by inhibiting the IL-6/gp130/JAK2/STAT3 signaling pathway. The compound is orally active and shows low toxicity. It has been studied for its potential in treating inflammatory diseases, including periodontitis and other conditions driven by IL-6 signaling. Detailed in vivo efficacy data are not extensively reported in the available literature. |
| Enzyme Assay |
Non-cell-based assays for LMT-28 typically involve binding studies to confirm its interaction with gp130. Surface plasmon resonance (SPR) or biolayer interferometry (BLI) can be used to measure the direct binding affinity of LMT-28 to purified gp130 protein. In vitro kinase assays using purified JAK2 may be performed to confirm inhibition of JAK2 activity, though LMT-28's primary mechanism is through gp130 binding rather than direct JAK2 inhibition.
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| Cell Assay |
Cell proliferation analysis [1] Cell erythroid cell line TF-1 phosphorylation [1].
Cell Types: TF-1 cells (1 ng/mL IL-6 induced) Tested Concentrations: 1, 10, 100, 1000, 10000 nM Incubation Duration: 72 hrs (hours) Experimental Results: Dramatically inhibited IL-6-induced TF-1 proliferation, IC50 The value is 7.5 μM. Western Blot Analysis[1] Cell Types: HepG2 cells (treated with 10 ng/mL IL-6) Tested Concentrations: 1, 3, 10, 30 and 100 μM Incubation Duration: 1 hour Experimental Results: Inhibition of IL-6-induced phosphorylated STAT3 , JAK2 and gp130. Cellular assays for LMT-28 utilize cells that respond to IL-6 stimulation. Cells are pre-treated with the compound at various concentrations, then stimulated with IL-6. The phosphorylation of STAT3, JAK2, and gp130 is assessed by Western blotting using phospho-specific antibodies. Downstream effects, such as STAT3-mediated gene expression (e.g., SOCS3, MCP-1), can be measured by qPCR. The compound's selectivity is confirmed by testing its effects on other cytokines such as IL-1β, TNF-α, or IFN-γ. |
| Animal Protocol |
Animal/Disease Models: Sixweeks old male DBA/1J mice (collagen-induced arthritis mice, CIA) [1]
Doses: 0-0.5 mg/kg Route of Administration: Oral; one time/day for 15 days Experimental Results: Serum cartilage Oligomeric matrix protein (COMP) levels were Dramatically diminished by 50%, serum amyloid P (SAP) levels were Dramatically diminished by 55%, and anti-CII IgG levels were Dramatically diminished by 62%. In vivo animal models for LMT-28 include models of IL-6-driven inflammation, such as periodontitis, rheumatoid arthritis, and bone resorption. The compound is administered orally at various doses (e.g., 0.25 or 1 mg/kg). Efficacy is assessed by measuring inflammatory markers in serum or tissues, bone resorption parameters, and histological examination of affected tissues. Detailed protocols are not extensively reported. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of LMT-28 include a molecular weight of 311.42 g/mol and molecular formula C17H29NO4. CAS number is 1239600-18-0. The compound is orally active. Purity is 98.93%. It is soluble in DMSO. Detailed PK parameters such as half-life and bioavailability are not extensively reported.
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| Toxicity/Toxicokinetics |
LMT-28 shows low toxicity. Detailed toxicological data are not extensively reported, but the compound has been evaluated in preclinical models with favorable safety profiles. As a research compound, its safety profile would need to be established through standard preclinical toxicity assessments. The compound is supplied for research use only. Given its mechanism of IL-6 inhibition, potential effects on immune function and host defense would be key safety considerations.
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| References | |
| Additional Infomation |
LMT-28 is a first-in-class, orally active, synthetic small-molecule inhibitor of IL-6 signaling that functions through direct binding to gp130. It has CAS number 1239600-18-0. It selectively inhibits IL-6-induced phosphorylation of STAT3, JAK2, and gp130. It shows low toxicity. It is used as a research tool for studying IL-6 biology and as a potential therapeutic agent for inflammatory diseases. It is for research use only.**
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| Molecular Formula |
C17H29NO4
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| Molecular Weight |
311.42
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| Exact Mass |
311.209
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| CAS # |
1239600-18-0
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| PubChem CID |
49846977
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| Appearance |
Colorless to light yellow viscous liquid
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
452.9±38.0 °C at 760 mmHg
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| Flash Point |
227.7±26.8 °C
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| Vapour Pressure |
0.0±2.5 mmHg at 25°C
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| Index of Refraction |
1.493
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| LogP |
3.05
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
22
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| Complexity |
419
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| Defined Atom Stereocenter Count |
3
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| SMILES |
O1C(N(C([C@@H](C)[C@@H](C(=C)CCCCC)O)=O)[C@H](C1)C(C)C)=O
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| InChi Key |
UDXWSYOXIRPYFK-RRFJBIMHSA-N
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| InChi Code |
InChI=1S/C17H29NO4/c1-6-7-8-9-12(4)15(19)13(5)16(20)18-14(11(2)3)10-22-17(18)21/h11,13-15,19H,4,6-10H2,1-3,5H3/t13-,14+,15+/m0/s1
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| Chemical Name |
(4S)-3-[(2S,3S)-3-hydroxy-2-methyl-4-methylidenenonanoyl]-4-propan-2-yl-1,3-oxazolidin-2-one
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| Synonyms |
LMT28 LMT 28 LMT-28
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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 : ~100 mg/mL (~321.11 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (8.03 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (8.03 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2111 mL | 16.0555 mL | 32.1110 mL | |
| 5 mM | 0.6422 mL | 3.2111 mL | 6.4222 mL | |
| 10 mM | 0.3211 mL | 1.6055 mL | 3.2111 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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