L006235

• CAT Number: I007546
• CAS Number: 294623-49-7
• Molecular Formula: C24H30N6O2S
• Molecular Weight: 466.604
• Purity: ≥95%
• Target: Cathepsin
• Solubility: Soluble in DMSO, not in water
• Storage: Store at 4°C
• IUPAC Name: N-[1-(cyanomethylcarbamoyl)cyclohexyl]-4-[2-(4-methylpiperazin-1-yl)-1,3-thiazol-4-yl]benzamide
• InChI: InChI=1S/C24H30N6O2S/c1-29-13-15-30(16-14-29)23-27-20(17-33-23)18-5-7-19(8-6-18)21(31)28-24(9-3-2-4-10-24)22(32)26-12-11-25/h5-8,17H,2-4,9-10,12-16H2,1H3,(H,26,32)(H,28,31)
• InChIKey: FIVYCSWOCXEWSE-UHFFFAOYSA-N
• SMILES: CN1CCN(CC1)C2=NC(=CS2)C3=CC=C(C=C3)C(=O)NC4(CCCCC4)C(=O)NCC#N

L006235(CAT: I007546) is a highly potent and selective inhibitor of cathepsin K, which is a lysosomal cysteine protease involved in bone resorption. It has an IC50 value of 0.25 nM for cathepsin K and exhibits over 4,000-fold selectivity over other cathepsin family members, including cathepsins B, L, and S. This selectivity profile makes L006235 a valuable tool for studying the biological functions of cathepsin K and for developing new therapies for diseases involving excessive bone resorption, such as osteoporosis.

Reference

1:J Biomed Mater Res B Appl Biomater. 2017 Jan;105(1):136-144. doi: 10.1002/jbm.b.33481. Epub 2015 Oct 5. Local co-delivery of rhBMP-2 and cathepsin K inhibitor L006235 in poly(d,l-lactide-co-glycolide) nanospheres.Yu NY,Fathi A,Murphy CM,Mikulec K,Peacock L,Cantrill LC,Dehghani F,Little DG,Schindeler A, PMID: 26435360 DOI: 10.1002/jbm.b.33481
Abstract: Cathepsin K inhibitors (CKIs) are an emerging class of drugs that are potent antagonists of osteoclastic activity. We speculated that they may be beneficial in bone tissue engineering, where a stress shielded environment can lead to rapid resorption of new bone. Most CKIs require frequent dosing, so to achieve a sustained release we manufactured polymer nanoparticles encapsulating the CKI L006235 (CKI/nP). CKI/nP and the collagen matrices that were used to deliver them were characterized by electron microscopy and fluorescent confocal microscopy, and data indicated that the particles were evenly distributed throughout the collagen. Elution studies indicated a linear release of the inhibitor from the CKI/nP, with approximately 2% of the drug being released per day. In an in vivo study, mice were implanted with collagen scaffolds containing rhBMP-2 that were loaded with the CKI/nP. Measurement of bone volume (BV) by microCT showed no significant increase with CKI/nP incorporation, and other parameters similarly showed no statistical differences. Cell culture studies confirmed the activity of the drug, even at low concentrations. These data indicate that polymer nanoparticles are an effective method for sustained drug delivery of a CKI, however, this may not be readily translatable to substantively improved bone tissue engineering outcomes. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 136-144, 2017.© 2015 Wiley Periodicals, Inc.