Cathepsin L Inhibitor (Z-FY-CHO) is a compound that can specifically inhibit the activity of Cathepsin L (Ki = 0.185nM) and is used to study the role of Cathepsin L in lysosomal function and protein degradation within cells[1]. Cathepsin L Inhibitor can bind to the active site of Cathepsin L, preventing its hydrolytic action on substrates, thereby regulating the metabolic balance of proteins within the cell[2]. Cathepsin L Inhibitor can be used to study the mechanisms of action of Cathepsin L in autophagy, apoptosis, and signal transduction in cells, helping to reveal the functions of Cathepsin L in physiological and pathological processes[3]. Cathepsin L Inhibitor also has potential anti-tumor effects, inhibiting the invasion and metastasis of tumor cells[4].
In vitro, pre-treatment of prostate cancer cells (LNCaP, C4-2) with Cathepsin L Inhibitor (5μM) for 30 minutes to 48 hours significantly inhibits cell migration and proliferation, while reducing STAT3 phosphorylation and Snail expression[5]. Pre-treatment of prostate cancer cells (ARCaP-M, ARCaP-Snail) and breast cancer cells (MDA-MB-468, MCF-7) with Cathepsin L Inhibitor (1–20μM) for 72 hours significantly inhibits the expression of Snail and vimentin, while restoring the expression of E-cadherin, inducing mesenchymal-to-epithelial transition (MET), and reducing cell migration and invasion capabilities[6].
In vivo, daily intraperitoneal injection of Cathepsin L Inhibitor (2.5–10mg/kg) in ovariectomized mice for 4 weeks significantly inhibits bone weight loss and reduces hydroxyproline content, while inhibiting collagen degradation[7]. Daily intraperitoneal injection of Cathepsin L Inhibitor (5mg/kg) in DSS-induced colitis mice for 7 days significantly alleviates body weight loss, colon shortening, and histological scores in colitis mice, while improving inflammatory symptoms[8].
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] Burton LJ, Smith BA, Smith BN, et al. Muscadine grape skin extract can antagonize Snail-cathepsin L-mediated invasion, migration and osteoclastogenesis in prostate and breast cancer cells. Carcinogenesis. 2015 Sep;36(9):1019-27.
[3] Li L, Gao L, Song Y, et al. Activated cathepsin L is associated with the switch from autophagy to apoptotic death of SH-SY5Y cells exposed to 6-hydroxydopamine. Biochem Biophys Res Commun. 2016 Feb 12;470(3):579-585.
[4] Xiong Y, Ji W, Fei Y, et al. Cathepsin L is involved in X-ray-induced invasion and migration of human glioma U251 cells. Cell Signal. 2017 Jan;29:181-191.
[5] Henderson VM, Hawsawi O, Burton LJ, et al. Cancer-bone microenvironmental interactions promotes STAT3 signaling. Mol Carcinog. 2019 Aug;58(8):1349-1361.
[6] Burton LJ, Dougan J, Jones J, et al. Targeting the Nuclear Cathepsin L CCAAT Displacement Protein/Cut Homeobox Transcription Factor-Epithelial Mesenchymal Transition Pathway in Prostate and Breast Cancer Cells with the Z-FY-CHO Inhibitor. Mol Cell Biol. 2017 Feb 15;37(5):e00297-16.
[7] Woo JT, Yamaguchi K, Hayama T, et al. Suppressive effect of N-(benzyloxycarbonyl)-L-phenylalanyl-L-tyrosinal on bone resorption in vitro and in vivo. Eur J Pharmacol. 1996 Apr 4;300(1-2):131-5.
[8] Menzel K, Hausmann M, Obermeier F, et al. Cathepsins B, L and D in inflammatory bowel disease macrophages and potential therapeutic effects of cathepsin inhibition in vivo. Clin Exp Immunol. 2006 Oct;146(1):169-80.
Cathepsin L Inhibitor (Z-FY-CHO)是一种能够特异性抑制Cathepsin L活性的化合物（Ki=0.185nM），用于研究Cathepsin L在细胞内溶酶体功能和蛋白质降解过程中的作用[1]。Cathepsin L Inhibitor可以与Cathepsin L的活性位点结合，阻止其对底物的水解作用，从而调节细胞内蛋白质的代谢平衡[2]。Cathepsin L Inhibitor可用于研究Cathepsin L在细胞自噬、细胞凋亡以及细胞信号传导中的作用机制，帮助揭示Cathepsin L在细胞生理和病理过程中的功能[3]。Cathepsin L Inhibitor还具有潜在的抗肿瘤作用，可抑制肿瘤细胞的侵袭和转移[4]。
在体外，Cathepsin L Inhibitor（5μM）预处理前列腺癌细胞（LNCaP、C4-2）30分钟至48小时，Cathepsin L Inhibitor显著抑制细胞迁移和增殖，同时降低STAT3磷酸化及Snail表达[5]。Cathepsin L Inhibitor（1–20μM）预处理前列腺癌细胞（ARCaP-M、ARCaP-Snail）及乳腺癌细胞（MDA-MB-468、MCF-7）72小时，Cathepsin L Inhibitor显著抑制Snail和波形蛋白（Vimentin）的表达，同时恢复E-钙黏蛋白（E-cadherin）的表达，诱导间质-上皮转化（MET），并降低细胞迁移和侵袭能力[6]。
在体内，Cathepsin L Inhibitor（2.5–10mg/kg）每日腹腔注射处理卵巢切除小鼠4周，显著抑制骨重量损失和羟基脯氨酸含量降低，同时抑制胶原降解[7]。Cathepsin L Inhibitor（5mg/kg）每日腹腔注射处理DSS诱导结肠炎小鼠7天，Cathepsin L Inhibitor显著减轻结肠炎小鼠体重下降、结肠缩短和组织学评分，同时改善炎症症状[8]。