Cathepsin S inhibitor
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
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 .
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 .
 Wiener JJ, Sun S, Thurmond RL. Recent advances in the design of cathepsin S inhibitors. Curr Top Med Chem. 2010;10(7):717-32.
 Lee-Dutra A, Wiener DK, Sun S. Cathepsin S inhibitors: 2004-2010. Expert Opin Ther Pat. 2011;21(3):311-37.
|Storage||Store at -20°C|
|Solubility||≥24.25 mg/mL in DMSO, <2.47 mg/mL in EtOH, <2.13 mg/mL in H2O|
|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|
|Shipping Condition||Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|
|Kinase experiment :|
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 :|
Mouse model of abdominal aortic aneurysm (AAA)
1, 3, 10, and 30 mg/kg, oral, BID dosing
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.
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.
 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.
|A slow, tight-binding reversible inhibitor of recombinant cathepsin S (Ki = 185 pM). Exhibits about 410-fold greater selectivity for cathepsin S compared to cathepsin B (Ki = 76 nM).|