組織蛋白酶K(英語:Cathepsin K),是一種在人體中由CTSK基因編碼的酶。[7][8]
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該基因編碼的蛋白質是半胱氨酸組織蛋白酶,一種參與骨重塑和再吸收的溶酶體半胱氨酸蛋白酶。這種蛋白質是肽酶C1蛋白質家族的成員,主要在破骨細胞中表達。
組織蛋白酶K是一種蛋白酶,其特徵在於其對激肽的高度特異性,與骨吸收有關。該酶分解代謝彈性蛋白、膠原蛋白和明膠的能力使其能夠分解骨骼和軟骨。這種分解代謝活動也是肺彈性喪失和肺氣腫反衝的部分原因。組織蛋白酶K抑制劑在骨質疏鬆症的治療中顯示出巨大的潛力。在被稱為受控組織蛋白酶同類相食的過程中,組織蛋白酶K被組織蛋白酶S降解。
組織蛋白酶K的表達受到組織損傷後釋放的炎性細胞因子的刺激。
組織蛋白酶K在很大一部分人類乳癌中表達,它可能有助於腫瘤侵襲性。[9]該基因的突變是緻密性成骨不全症的原因,這是一種以骨質硬化和身材矮小為特徵的常染色體隱性遺傳病。[10]組織蛋白酶K也被發現在膠質母細胞瘤中過度表達。[11]
組織蛋白酶K的表達是某些癌症的特徵,而其他癌症則沒有。[12]組織蛋白酶K抗體已上市銷售,用於研究該酶在各種細胞中的表達。[13][14][15]
默克公司在骨質疏鬆症的III期臨床試驗中使用了一種組織蛋白酶K抑制劑,奧達那替尼。2016年9月,默克公司在自行評估不良事件後宣佈停止開發奧達那替尼,獨立評估顯示中風風險增加。[16][17]其他組織蛋白酶K抑制劑處於不同的發展階段。[18][19]截至2017年10月,Medivir公司有一種組織蛋白酶K抑制劑MIV-711(L-006235[20][21][22]),在IIa期臨床試驗中,作為一種改善骨關節炎的藥物。
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Cathepsin K Antibodies. Novus Biologicals online catalog. Novus Biologicals, LLC. 2016 [2 October 2016]. (原始內容存檔於2022-10-31).
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Hussein, H., Ishihara, A., Menendez, M., & Bertone, A. (2014). Pharmacokinetics and bone resorption evaluation of a novel Cathepsin K inhibitor (VEL‐0230) in healthy adult horses. Journal of veterinary pharmacology and therapeutics.
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- Brömme D, Okamoto K. Human cathepsin O2, a novel cysteine protease highly expressed in osteoclastomas and ovary molecular cloning, sequencing and tissue distribution.. Biological Chemistry Hoppe-Seyler. 1995, 376 (6): 379–84. PMID 7576232. doi:10.1515/bchm3.1995.376.6.379.
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- Polymeropoulos MH, Ortiz De Luna RI, Ide SE, et al. The gene for pycnodysostosis maps to human chromosome 1cen-q21.. Nature Genetics. 1995, 10 (2): 238–9 [2022-10-31]. PMID 7663522. S2CID 11723845. doi:10.1038/ng0695-238. (原始內容存檔於2022-10-31).
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- Velasco G, Ferrando AA, Puente XS, et al. Human cathepsin O. Molecular cloning from a breast carcinoma, production of the active enzyme in Escherichia coli, and expression analysis in human tissues.. The Journal of Biological Chemistry. 1994, 269 (43): 27136–42. PMID 7929457. doi:10.1016/S0021-9258(18)47135-9 .
- Li YP, Alexander M, Wucherpfennig AL, et al. Cloning and complete coding sequence of a novel human cathepsin expressed in giant cells of osteoclastomas.. Journal of Bone and Mineral Research. 1996, 10 (8): 1197–202. PMID 8585423. S2CID 41832979. doi:10.1002/jbmr.5650100809.
- Bossard MJ, Tomaszek TA, Thompson SK, et al. Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification.. Journal of Biological Chemistry. 1996, 271 (21): 12517–24. PMID 8647860. doi:10.1074/jbc.271.21.12517 .
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- Johnson MR, Polymeropoulos MH, Vos HL, et al. A nonsense mutation in the cathepsin K gene observed in a family with pycnodysostosis.. Genome Research. 1997, 6 (11): 1050–5. PMID 8938428. doi:10.1101/gr.6.11.1050 .
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- Rood JA, Van Horn S, Drake FH, et al. Genomic organization and chromosome localization of the human cathepsin K gene (CTSK).. Genomics. 1997, 41 (2): 169–76. PMID 9143491. doi:10.1006/geno.1997.4614.
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