Cathepsin K
Cathepsin K (CTSK) is a lysosomal cysteine protease highly expressed by bone-resorbing osteoclasts and shows potent collagenase activity in bone matrix degradation[1]. Mechanistically, CTSK supports osteoclastic resorption because it cleaves collagen I, whereas cathepsins B, S, and L show weaker or non-detected roles in osteoclast bone resorption contexts[2]. Heparan sulfate regulates CTSK by forming stable complexes, inducing dimerization, preserving peptidase activity, and selectively inhibiting collagenase activity without blocking the active site[3]. In osteoarthritis research, CTSK links to cartilage degradation through type II collagen cleavage, with increased serum CTSK in patients and upregulated CTSK in degraded cartilage in animal models[4]. In periodontitis models, CTSK inhibition with odanacatib reduced osteoclasts, macrophages, T cells, Toll-like receptor expression, bone loss, and immune activation[5]. Compared with related isoforms, CTSK has distinctive collagenolytic activity and selectivity challenges because homologous CTSK/S binding sites can cause unselective inhibition[6]. For experimental applications, CTSK inhibitors, heparan sulfate oligosaccharides, and light-activated inhibitors provide tools to study bone resorption, cartilage degradation, and collagen I degradation in 3D tumor spheroids[3][4][7].
References:
- [1]. Guan X, et al. Small-molecule Cathepsin K inhibitors: a medicinal chemistry perspective. Future Med Chem. 2025 Jul;17(14):1757-1770. [Content Brief]
- [2]. Zaidi M, et al. Cathepsin K, osteoclastic resorption, and osteoporosis therapy. J Bone Miner Res. 2001 Oct;16(10):1747-9. [Content Brief]
- [3]. Zhang X, et al. Heparan sulfate selectively inhibits the collagenase activity of cathepsin K. Matrix Biol. 2024 May;129:15-28. [Content Brief]
- [4]. Brizuela L, et al. Cathepsin K Inhibitors as Potential Drugs for the Treatment of Osteoarthritis. Int J Mol Sci. 2025 Mar 22;26(7):2896. [Content Brief]
- [5]. Hao L, et al. Odanacatib, A Cathepsin K-Specific Inhibitor, Inhibits Inflammation and Bone Loss Caused by Periodontal Diseases. J Periodontol. 2015 Aug;86(8):972-83. [Content Brief]
- [6]. Khalili M, et al. Underserved Does Not Mean Undeserved: Unfurling the HCV Care in the Safety Net. Dig Dis Sci. 2018 Dec;63(12):3250-3252. [Content Brief]
- [7]. Herroon MK, et al. Photoactivated inhibition of cathepsin K in a 3D tumor model. Biol Chem. 2016 Jun 1;397(6):571-82. [Content Brief]
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Cathepsin K Related Products (22)
Related Products (22)
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Recombinant Proteins (1)
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Antibodies (1)
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Cathepsin K-IN-9
0 ImagesCat. No.: HY-179697CAS No.: 2361420-28-0Cathepsin K-IN-9 is a selective, potent and orally active Cathepsin K inhibitor with an IC50 of 6.2 nM. Cathepsin K-IN-9 has IC50 > 10000 nM for cathepsin B, L, and S, showing over 1600-fold selectivity. Cathepsin K-IN-9 has excellent safety and metabolic stability.Cathepsin K-IN-9 can be used for the research of osteoporosis.
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SARS-CoV-2 3CLpro-IN-34
0 ImagesCat. No.: HY-179612SARS-CoV-2 3CLpro-IN-34 (Compound 55) is a highly efficient non-covalent inhibitor of the SARS-CoV-2 3CLpro protease (b. SARS-CoV-2 3CLpro protease) with an IC50 of 1.9 μM. SARS-CoV-2 3CLpro-IN-34 can inhibit the 3CLpro protein of SARS-CoV-1, with its IC50 being 3.2 μM, and it shows high selectivity towards host cysteine proteases (such as cathepsins L/K and calpain). SARS-CoV-2 3CLpro-IN-34 exhibits antiviral activity in cells infected with SARS-CoV-2, with its EC50 being 25 μM, and it is not affected by P-gp inhibitors and shows no significant cytotoxicity. SARS-CoV-2 3CLpro-IN-34 can be used for research on SARS-CoV-2 infection.
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