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ML604440

Cat No.:V33780 Purity: ≥98%
ML604440 is a specific and cell-penetrable inhibitor of the proteasome β1i (LMP2) subunit.
ML604440
ML604440 Chemical Structure CAS No.: 1140517-08-3
Product category: New2
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
1mg
5mg
10mg
Other Sizes
Official Supplier of:
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Product Description
ML604440 is a specific and cell-penetrable inhibitor of the proteasome β1i (LMP2) subunit. ML604440 may be utilized in study/research of experimental colitis, EAE, and autoimmune diseases. ML604440 has synergistic effects when combined with LMP7 inhibitors.
Biological Activity I Assay Protocols (From Reference)
ln Vitro
In splenocytes from wt or LMP7-deficient mice, treatment with ML604440 (300 nM; overnight) had an impact on the surface expression of H-2Kb [2]. ML604440 treatment (300 nM; 24 hours) did not substantially stain human PBMC or mice splenocytes. ML604440 (300 nM; 3 days) had no influence on the overall quantity of CD4+ T cells that produce IL-17A [2].
ln Vivo
LMP2 is stained in vivo by ML604440 treatment (ip; 10 mg/kg; once daily; 7 days) without causing appreciable alterations to the projection behind it [3].
Animal Protocol
Animal/Disease Models: Male C57BL/6J mice (6-8 weeks old) were injected with anti-platelet monoclonal antibodies [3]
Doses: 10 mg/kg
Route of Administration: intraperitoneal (ip) injection; 10 mg/kg; one time/day; 7-day
Experimental Results: LMP2 is inhibited in vivo. There was no significant improvement in platelet counts after immunizing mice with a monoclonal rat anti-mouse CD41 platelet antibody.
References

[1]. Structure-based design of β1i or β5i specific inhibitors of human immunoproteasomes. J Med Chem. 2014 Jul 24;57(14):6197-209.

[2]. Co-inhibition of immunoproteasome subunits LMP2 and LMP7 is required to block autoimmunity. EMBO Rep. 2018 Dec;19(12). pii: e46512.

[3]. Co-Inhibition of the Immunoproteasome Subunits LMP2 and LMP7 Ameliorates Immune Thrombocytopenia. Front Immunol. 2021 Jan 20;11:603278.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C17H24BF3N2O4
Molecular Weight
388.189675331116
Exact Mass
388.178
CAS #
1140517-08-3
PubChem CID
57655545
Appearance
White to yellow solid powder
Hydrogen Bond Donor Count
4
Hydrogen Bond Acceptor Count
7
Rotatable Bond Count
7
Heavy Atom Count
27
Complexity
527
Defined Atom Stereocenter Count
1
SMILES
FC(C1C=CC=CC=1C(NC(C)(C)C(N[C@H](B(O)O)CC(C)C)=O)=O)(F)F
InChi Key
IRZZVDHGNHGNAI-ZDUSSCGKSA-N
InChi Code
InChI=1S/C17H24BF3N2O4/c1-10(2)9-13(18(26)27)22-15(25)16(3,4)23-14(24)11-7-5-6-8-12(11)17(19,20)21/h5-8,10,13,26-27H,9H2,1-4H3,(H,22,25)(H,23,24)/t13-/m0/s1
Chemical Name
[(1R)-3-methyl-1-[[2-methyl-2-[[2-(trifluoromethyl)benzoyl]amino]propanoyl]amino]butyl]boronic acid
HS Tariff Code
2934.99.9001
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)
Solubility Data
Solubility (In Vitro)
DMSO : ~100 mg/mL (~257.61 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.44 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 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 (6.44 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 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.44 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.5761 mL 12.8803 mL 25.7606 mL
5 mM 0.5152 mL 2.5761 mL 5.1521 mL
10 mM 0.2576 mL 1.2880 mL 2.5761 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.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

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  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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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