| Size | Price | Stock | Qty |
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| Targets |
LMP7 (immunoproteasome subunit beta5i). LMP7-IN-1 is a selective inhibitor of the immunoproteasome subunit LMP7 (beta5i). The immunoproteasome plays a role in antigen processing and immune responses. By inhibiting LMP7, the compound modulates immune responses, reducing inflammation and cytokine production.
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| ln Vitro |
M3258 inhibits LMP7 in humans with an IC50 of 4.1 nM on average. M3258 has little activity (average IC50=2519 nM) against constitutive proteasome subunit β5. With an IC50 ranging from 2 to 37 nM, M3258 potently inhibits LMP7 in human multiple myeloma cell lines MM.1S and U266B1 as well as in PBMC from dogs, rats, and humans [2]. With an EC50 of 1980 nM, M3258 increased the amount of ubiquitinated protein in MM.1S cells by more than fourfold. M3258 disrupts the immunoproteasome's activity. M3258 also lowers MM.1S cell viability (IC50=367 nM) and causes apoptosis as measured by caspase 3/7 activity (EC50=420 nM; >3.5-fold induction) [2].
LMP7-IN-1 has an IC₅0 of 3.6 nM against LMP7 biochemically and 3.4 nM in cells. The compound is a reversible and highly selective inhibitor of the immunoproteasome subunit LMP7 (beta5i). It leads to significant and prolonged suppression of tumor LMP7 activity and ubiquitinated protein turnover, inducing apoptosis in multiple myeloma cells. |
| ln Vivo |
M3258 (1 mg/kg; 10 mg/kg) compared to the licensed non-selective proteasome inhibitors bortezomib and ixazomib in selected multiple myeloma and mantle cell lymphoma xenograft models It has showed superior anti-tumor activity [2].
In vivo, LMP7-IN-1 is orally bioavailable and demonstrates potent anti-tumor activity in multiple myeloma xenograft models. The compound also shows potential for treating inflammatory and autoimmune diseases, neurodegenerative diseases, and proliferative diseases. |
| Enzyme Assay |
LMP7 enzymatic activity is measured using a fluorogenic peptide substrate assay. Recombinant LMP7 or immunoproteasome preparations are incubated with a peptide substrate and serial dilutions of test compound. Cleavage of the substrate generates a fluorescent signal, and IC₅0 values are calculated from dose-response curves.
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| Cell Assay |
Cell viability assay [2]
Cell Types: MM.1S Cell Tested Concentrations: 0.01-100 nM Incubation Duration: 2 hrs (hours) Experimental Results: Effectively inhibited LMP7 (IC50=2.2 nM) in the human multiple myeloma cell line MM.1S. Cells (e.g., multiple myeloma cells) are treated with LMP7-IN-1 at various concentrations. LMP7 activity is assessed by measuring substrate cleavage. Protein ubiquitination and turnover are evaluated by Western blotting. Apoptosis is measured by caspase-3/7 activation and Annexin V staining. Cell viability is assessed using MTT or CellTiter-Glo assays. |
| Animal Protocol |
Animal/Disease Models: Female H2d Rag2 mouse or female CB-17 SCID mouse (U266B1 subcutaneousxenograft model; MM.1S subcutaneousxenograft model) [2]
Doses: 1 mg/kg in U266B1 subcutaneousxenograft model; MM.1S 10 mg/kg dosed in subcutaneousxenograft model: Po; one time/day, once every two days, or twice weekly (days 1 and 4) Experimental Results: Demonstrated significant and powerful antitumor efficacy. Mice bearing multiple myeloma xenografts or other disease models are administered LMP7-IN-1 orally. Tumor growth is monitored by caliper measurements. Tumors are harvested for pharmacodynamic analysis of LMP7 inhibition, ubiquitinated protein accumulation, and apoptosis markers. Efficacy is determined by tumor growth inhibition and survival. |
| ADME/Pharmacokinetics |
LMP7-IN-1 has a molecular weight of 329.16 g/mol and formula C1₇H20BNO₅. As an orally bioavailable compound, it is expected to have favorable oral bioavailability. Standard PK parameters would be determined in rodent studies following PO and IV administration.
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| Toxicity/Toxicokinetics |
Toxicology data for LMP7-IN-1 are not publicly available. Standard preclinical safety assessment would include cytotoxicity screening, hERG testing, and repeat-dose toxicology studies in rodents. Given the role of the immunoproteasome in immune function, potential immunomodulatory effects would be carefully evaluated.
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| References |
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| Additional Infomation |
M3258, an LMP7 inhibitor, is an orally bioavailable, highly effective, selective, and reversible large multifunctional peptidase 7 (LMP7, β5i, PSMB8) inhibitor. LMP7 is a chymotrypsin-like proteolytic subunit of the immunoproteasome and possesses potential antitumor activity. After oral administration, M3258 targets and inhibits the proteolytic activity of the LMP7 subunit of the immunoproteasome, thereby blocking its deubiquitination activity. This blocks the ubiquitin-proteasome degradation pathway, preventing the degradation of defective proteins and leading to the accumulation of polyubiquitinated proteins. This induces the unfolded protein response (UPR), ultimately resulting in tumor cell apoptosis and tumor cell growth inhibition. The proteasome is a large multi-subunit protease complex capable of degrading ubiquitinated unwanted or damaged proteins, thereby restoring protein homeostasis. Unlike constitutive proteasomes expressed in most tissues, the immunoproteasome is specifically present in normal and malignant hematopoietic cells, including multiple myeloma cells. Immunoplasmosomes degrade ubiquitinated proteins to generate peptides for the presentation of MHC class I molecules, playing a key role in adaptive immune responses and inflammatory diseases.
LMP7-IN-1 (M3258) is a research compound for studying immunoproteasome biology. It is not clinically approved. The compound is useful for investigating the role of LMP7 in autoimmune diseases, inflammation, neurodegenerative diseases, and cancer. LMP7-IN-1 offers a promising therapeutic approach in autoimmune and inflammatory disorder treatment strategies. |
| Molecular Formula |
C17H20BNO5
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| Molecular Weight |
329.155405044556
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| Exact Mass |
329.143
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| CAS # |
2285330-15-4
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| PubChem CID |
138319683
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
24
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| Complexity |
476
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| Defined Atom Stereocenter Count |
4
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| SMILES |
O1[C@@H]2CC[C@H]1[C@H](C(N[C@H](B(O)O)CC1=COC3C=CC=CC1=3)=O)C2
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| InChi Key |
RFQDLTYXNINJON-OYNZBZHQSA-N
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| InChi Code |
InChI=1S/C17H20BNO5/c20-17(13-8-11-5-6-15(13)24-11)19-16(18(21)22)7-10-9-23-14-4-2-1-3-12(10)14/h1-4,9,11,13,15-16,21-22H,5-8H2,(H,19,20)/t11-,13-,15+,16+/m1/s1
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| Chemical Name |
[(1R)-2-(1-benzofuran-3-yl)-1-[[(1S,2R,4R)-7-oxabicyclo[2.2.1]heptane-2-carbonyl]amino]ethyl]boronic acid
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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 : ~250 mg/mL (~759.51 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (6.32 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (6.32 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 | 3.0380 mL | 15.1902 mL | 30.3804 mL | |
| 5 mM | 0.6076 mL | 3.0380 mL | 6.0761 mL | |
| 10 mM | 0.3038 mL | 1.5190 mL | 3.0380 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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