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Cathepsin S inhibitor (Synonyms: LY 3000328)

Catalog No.GC14903

A potent cathepsin S inhibitor

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Cathepsin S inhibitor Chemical Structure

Cas No.: 1373215-15-6

Size Price Stock Qty
10mM (in 1mL DMSO)
$131.00
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1mg
$55.00
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2mg
$82.00
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5mg
$123.00
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10mg
$160.00
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50mg
$390.00
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100mg
$545.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

View current batch:

Protocol

Kinase experiment [1]:

Kinase assays

Assays were performed for Cat S, mCat S, Cat B and Cat L by adding enzyme to a concentration of FRET substrate equal to the Km in a 50 mM sodium phosphate buffer (pH 6.5) containing 2.5 mM DTT, 2.5 mM EDTA plus 0.01% Triton X-100. The Cat V and Cat K assays were performed as above, but in a 0.1 M sodium acetate (pH 5.5) buffer containing 2.5 mM DTT, 2.5 mM EDTA plus 0.01% Triton X-100. Km values for the FRET substrate were 25 μM, 25 μM, 20 μM, 37.5 μM, 35 μM, 35 μM and 25 μM for human Cat S, mouse Cat S, human Cat L, human Cat B, human Cat K, human Cat V and human Cat F respectively.

Animal experiment [1]:

Animal models

Mouse model of abdominal aortic aneurysm (AAA)

Dosage form

1, 3, 10, and 30 mg/kg, oral, BID dosing

Application

The efficacies of Cathepsin S inhibitor was studied in a mouse model of abdominal aortic aneurysm (AAA). Cathepsin S inhibitor exhibited a dose-responsive aortic diameter reduction at 1, 3, 10, and 30 mg/kg. At the lowest dose of 1 mg/kg of Cathepsin S inhibitor, the aortic diameter is reduced by 58%, then 83% at 3 mg/kg, and 87% at 10 mg/kg.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Jadhav PK, et al. Discovery of Cathepsin S Inhibitor LY3000328 for the Treatment of Abdominal Aortic Aneurysm. ACS Med Chem Lett. 2014 Aug 27;5(10):1138-42.

Background

Ki: 0.185 nM

Cathepsin S is a lysosomal cysteine protease, playing an important role in antigen presentation. The inhibition of Cathepsin S is expected to result in immunosuppression, which makes this enzyme an attractive target to potentially treat autoimmune and inflammatory diseases. Cathepsin S inhibitor is a novel Cathepsin S inhibitor.

In vitro: Cathepsin S inhibitor was a slow, tight-binding reversible inhibitor of recombinant cathepsin S, exhibiting greater selectivity for cathepsin S compared to cathepsin B [1].

In vivo: No animal in vivo data available currently

Clinical trial: Oral Cathepsin S inhibitor that blocked MHCII antigen presentation could result in a T-cell-selective immunosuppressant agent with improved safety over the current standard of care for the treatment of rheumatoid arthritis, psoriasis, multiple sclerosis and other autoimmune-based inflammatory diseases [2].

References:
[1] Wiener JJ, Sun S, Thurmond RL.  Recent advances in the design of cathepsin S inhibitors. Curr Top Med Chem. 2010;10(7):717-32.
[2] Lee-Dutra A, Wiener DK, Sun S.  Cathepsin S inhibitors: 2004-2010. Expert Opin Ther Pat. 2011;21(3):311-37.

Chemical Properties

Cas No. 1373215-15-6 SDF
Synonyms LY 3000328
Chemical Name [(3R,4S)-4-[(4-fluorobenzoyl)amino]-6-[4-(oxetan-3-yl)piperazin-1-yl]-3,4-dihydro-2H-chromen-3-yl] N-methylcarbamate
Canonical SMILES CNC(=O)OC1COC2=C(C1NC(=O)C3=CC=C(C=C3)F)C=C(C=C2)N4CCN(CC4)C5COC5
Formula C25H29FN4O5 M.Wt 484.52
Solubility ≥ 24.25 mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 2.0639 mL 10.3195 mL 20.639 mL
5 mM 0.4128 mL 2.0639 mL 4.1278 mL
10 mM 0.2064 mL 1.0319 mL 2.0639 mL
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In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

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