2. Metabolic Enzyme/Protease Apoptosis
  3. Proteasome Apoptosis
  4. M3258

M3258 is an orally bioavailable, potent, reversible and highly selective immunoproteasome subunit LMP7 (β5i) inhibitor. M3258 exerts high biochemical (IC50=3.6 nM) and cellular (IC50=3.4 nM) potency against the LMP7 subunit. M3258 shows strong antitumor efficacy in multiple myeloma xenograft models. M3258 leads to a significant and prolonged suppression of tumor LMP7 activity and ubiquitinated protein turnover and the induction of apoptosis in multiple myeloma cells.

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M3258

M3258 Estructura química

No. CAS : 2285330-15-4

Tamaño Precio Stock Cantidad
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 En stock
Solution
10 mM * 1 mL in DMSO En stock
Solid
5 mg En stock
10 mg En stock
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100 mg En stock
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500 mg   Obtener un presupuesto  

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Based on 5 publication(s) in Google Scholar

M3258 Related Antibodies

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Descripciòn

M3258 is an orally bioavailable, potent, reversible and highly selective immunoproteasome subunit LMP7 (β5i) inhibitor. M3258 exerts high biochemical (IC50=3.6 nM) and cellular (IC50=3.4 nM) potency against the LMP7 subunit. M3258 shows strong antitumor efficacy in multiple myeloma xenograft models. M3258 leads to a significant and prolonged suppression of tumor LMP7 activity and ubiquitinated protein turnover and the induction of apoptosis in multiple myeloma cells[1][2].

IC50 & Target

LMP7[1]
Cellular Effect
Cell Line Type Value Description References
HepG2 IC50
48 3
Compound: 50
Cytotoxicity against human HepG2 cells assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
Cytotoxicity against human HepG2 cells assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
[PMID: 34228444]
Hepatocyte IC50
91 3
Compound: 50
Cytotoxicity against human primary hepatocytes assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
Cytotoxicity against human primary hepatocytes assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
[PMID: 34228444]
Hepatocyte IC50
64 3
Compound: 50
Cytotoxicity against Wistar Han rat hepatocytes assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
Cytotoxicity against Wistar Han rat hepatocytes assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
[PMID: 34228444]
Hepatocyte IC50
91 3
Compound: 50
Cytotoxicity against human primary hepatocytes assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
Cytotoxicity against human primary hepatocytes assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
[PMID: 34228444]
Hepatocyte IC50
64 3
Compound: 50
Cytotoxicity against Wistar Han rat hepatocytes assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
Cytotoxicity against Wistar Han rat hepatocytes assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
[PMID: 34228444]
HepG2 IC50
48 3
Compound: 50
Cytotoxicity against human HepG2 cells assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
Cytotoxicity against human HepG2 cells assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
[PMID: 34228444]
HepG2 IC50
48 3
Compound: 50
Cytotoxicity against human HepG2 cells assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
Cytotoxicity against human HepG2 cells assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
[PMID: 34228444]
Hepatocyte IC50
64 3
Compound: 50
Cytotoxicity against Wistar Han rat hepatocytes assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
Cytotoxicity against Wistar Han rat hepatocytes assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
[PMID: 34228444]
Hepatocyte IC50
91 3
Compound: 50
Cytotoxicity against human primary hepatocytes assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
Cytotoxicity against human primary hepatocytes assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
[PMID: 34228444]
In Vitro

M3258 inhibits human LMP7 with a mean IC50 of 4.1 nM. M3258 displays weak activity against the constitutive proteasome subunit β5 (mean IC50=2519 nM). M3258 potently inhibits LMP7 in the human multiple myeloma cell lines MM.1S and U266B1 and in human, rat, and dog PBMCs with IC50s between 2 and 37 nM[2].
M3258 induces a >four fold accumulation of ubiquitinated proteins with an EC50 of 1980 nM in MM.1S cells. M3258 interferes with immunoproteasome function. M3258 also induces apoptosis assessed by caspase 3/7 activity (EC50=420 nM;>3.5-fold induction) and reduces MM.1S cell viability (IC50=367 nM)[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

M3258 Related Antibodies

Cell Viability Assay[2]

Cell Line: MM.1S cells
Concentration: 0.01-100 nM
Incubation Time: 2 hours
Result: Potently inhibited LMP7 in the human multiple myeloma cell lines MM.1S (IC50=2.2 nM).
In Vivo

M3258 (1 mg/kg; 10 mg/kg) shows superior antitumor efficacy in selected multiple myeloma and mantle cell lymphoma xenograft models compared with the approved nonselective proteasome inhibitors bortezomib and ixazomib[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Female H2d Rag2 mice or female CB-17 SCID mice (U266B1 subcutaneous xenograft model; MM.1S subcutaneous xenograft model)[2]
Dosage: 1 mg/kg in U266B1 subcutaneous xenograft model; 10 mg/kg in MM.1S subcutaneous xenograft model
Administration: P.o.; either once daily, every 2 days or twice weekly (days 1 and 4)
Result: Displayed significant and strong antitumor efficacy.
Ensayo clínico
Peso molecular

329.16

Fòrmula

C17H20BNO5
No. CAS
Appearance

Solid

Color

White to off-white

SMILES

O=C(N[C@@H](CC1=COC2=C1C=CC=C2)B(O)O)[C@H]3[C@@H]4CC[C@@H](O4)C3
Envío

Room temperature in continental US; may vary elsewhere.
Almacenamiento
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvente y solubilidad
In Vitro: 

DMSO : 250 mg/mL (759.51 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 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
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

  • Calculadora de molaridad

  • Calculadora de dilución

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.08 mg/mL (6.32 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.08 mg/mL (6.32 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación

Purity: 98.0%

SDS (251 KB)

COA (260 KB) HNMR (265 KB)

Instrucciones de manejo (2659 KB)
Referencias

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 3.0380 mL 15.1902 mL 30.3804 mL 75.9509 mL
5 mM 0.6076 mL 3.0380 mL 6.0761 mL 15.1902 mL
10 mM 0.3038 mL 1.5190 mL 3.0380 mL 7.5951 mL
15 mM 0.2025 mL 1.0127 mL 2.0254 mL 5.0634 mL
20 mM 0.1519 mL 0.7595 mL 1.5190 mL 3.7975 mL
25 mM 0.1215 mL 0.6076 mL 1.2152 mL 3.0380 mL
30 mM 0.1013 mL 0.5063 mL 1.0127 mL 2.5317 mL
40 mM 0.0760 mL 0.3798 mL 0.7595 mL 1.8988 mL
50 mM 0.0608 mL 0.3038 mL 0.6076 mL 1.5190 mL
60 mM 0.0506 mL 0.2532 mL 0.5063 mL 1.2658 mL
80 mM 0.0380 mL 0.1899 mL 0.3798 mL 0.9494 mL
100 mM 0.0304 mL 0.1519 mL 0.3038 mL 0.7595 mL
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M3258 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

M32582285330-15-4M 3258M-3258ProteasomeApoptosisantitumorMM.1SmultiplemyelomaimmunoproteasomeoralselectiveInhibitorinhibitorinhibit

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Nombre del producto:
M3258
Cat. No.:
HY-111790
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