| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
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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].
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| 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].
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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. |
| 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. |
| References |
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| Additional Infomation |
LMP7 Inhibitor M3258 is an orally bioavailable, potent, selective, reversible inhibitor of the large multifunctional peptidase 7 (LMP7, Beta5i, PSMB8), a chymotrypsin-like, proteolytic subunit of the immunoproteasome, with potential antineoplastic activity. Upon oral administration, LMP7 inhibitor M3258 targets and inhibits the proteolytic activity of the LMP7 subunit of immunoproteasome, thereby blocking its deubiquitylating activity. This blocks the ubiquitin proteasome degradation pathway, prevents the degradation of defective proteins, and leads to an accumulation of poly-ubiquitylated proteins. This induces the unfolded protein response (UPR) and results in both the induction of tumor cell apoptosis and the inhibition of tumor cell growth. Proteasomes are large multi-subunit protease complexes that degrade unneeded or damaged proteins that have been ubiquitinated, thereby restoring protein homeostasis. Unlike the constitutive proteasome, which is expressed in most tissues, immunoproteasome is specifically present in normal and malignant hematopoietic cells, including multiple myeloma. Immunoproteasome degrades ubiquitinated proteins, generates peptides for presentation on MHC class I, and plays a key role in the adaptive immune response and inflammatory diseases.
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| 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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