Odanacatib (MK-0822)是一种具有口服活性的组织蛋白酶K（Cathepsin K）抑制剂。
Cas No.:603139-19-1
Sample solution is provided at 25 µL, 10mM.
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Odanacatib (MK-0822) is an orally active inhibitor of cathepsin K. Odanacatib reduces bone resorption by inhibiting cathepsin K in osteoclasts, while relatively preserving bone formation[1-2]. Odanacatib can be used for the treatment and related research of osteoporosis[3-4].
In vitro, Odanacatib (2μM) was used to treat human renal carcinoma Caki cells for 6-24 hours, followed by co-treatment with TRAIL (50ng/ml). Odanacatib significantly induced cell apoptosis and c-PARP cleavage, while enhancing the sensitivity of cancer cells to anticancer drugs[5]. Odanacatib alone (2-10μM) or in combination with a low dose of oxaliplatin (25μM) was used to treat human renal carcinoma Caki-1, ACHN cells, glioma U87MG cells, and breast cancer MCF7 cells for 24-48 hours. Odanacatib significantly induced apoptosis (increased sub-G1 phase cells) and PARP cleavage, while upregulating the expression of the pro-apoptotic protein Bax[6].
In vivo, Odanacatib (3.606mg/kg/week) was administered orally to male BALB/cJ mice, starting one week before establishing a periapical disease model and continuing for 6 weeks. Odanacatib significantly inhibited bone resorption in the lesion area, while reducing the infiltration of macrophages and T cells, as well as the expression of pro-inflammatory cytokines and Toll-like receptors[7]. In a collagen-induced arthritis model, Odanacatib (10mg/kg/day) was orally administered to female DBA/1 mice, starting on day 27 after disease induction and continuing for 21 days. Odanacatib significantly reduced serum markers of bone and cartilage degradation (CTX I and CTX II)[8].
References:
[1] Boggild MK, Gajic-Veljanoski O, McDonald-Blumer H, et al. Odanacatib for the treatment of osteoporosis. Expert Opin Pharmacother. 2015;16(11):1717-26.
[2] Chapurlat RD. Odanacatib: a review of its potential in the management of osteoporosis in postmenopausal women. Ther Adv Musculoskelet Dis. 2015 Jun;7(3):103-9.
[3] Khosla S, Hofbauer LC. Osteoporosis treatment: recent developments and ongoing challenges. Lancet Diabetes Endocrinol. 2017 Nov;5(11):898-907.
[4] Schultz TC, Valenzano JP, Verzella JL, et al. Odanacatib: an emerging novel treatment alternative for postmenopausal osteoporosis. Womens Health (Lond). 2015 Nov;11(6):805-14.
[5] Seo SU, Woo SM, Kim MW, et al. Cathepsin K inhibition-induced mitochondrial ROS enhances sensitivity of cancer cells to anti-cancer drugs through USP27x-mediated Bim protein stabilization. Redox Biol. 2020 Feb;30:101422.
[6] Seo SU, Woo SM, Kim S, et al. Inhibition of cathepsin K sensitizes oxaliplatin-induced apoptotic cell death by Bax upregulation through OTUB1-mediated p53 stabilization in vitro and in vivo. Oncogene. 2022 Jan;41(4):550-559.
[7] Hao L, Chen W, McConnell M, et al. A small molecule, odanacatib, inhibits inflammation and bone loss caused by endodontic disease. Infect Immun. 2015 Apr;83(4):1235-45.
[8] Panwar P, Andrault PM, Saha D, et al. Immune regulatory and anti-resorptive activities of tanshinone IIA sulfonate attenuates rheumatoid arthritis in mice. Br J Pharmacol. 2024 Dec;181(24):5009-5027.
Odanacatib (MK-0822)是一种具有口服活性的组织蛋白酶K（Cathepsin K）抑制剂。Odanacatib可通过抑制破骨细胞中的组织蛋白酶K来减少骨吸收，同时相对保留骨形成[1-2]。Odanacatib可用于骨质疏松症的治疗和相关研究[3-4]。
在体外，Odanacatib（2μM）处理人肾癌Caki细胞6-24小时，随后与TRAIL（50ng/ml）联合处理。Odanacatib显著诱导细胞凋亡和c-PARP切割，同时增强癌细胞对抗癌药物的敏感性[5]。Odanacatib单独处理（2-10μM）或与低剂量奥沙利铂（25μM）联合处理人肾癌Caki-1、ACHN细胞、胶质瘤U87MG细胞及乳腺癌MCF7细胞24-48小时。Odanacatib显著诱导细胞凋亡（亚G1期细胞增多）和PARP切割，同时上调促凋亡蛋白Bax的表达[6]。
在体内，Odanacatib（3.606mg/kg/week）经口腔给药处理雄性BALB/cJ小鼠，从建立根尖周病模型前1周开始给药直至6周。Odanacatib显著抑制了病变区域的骨吸收，同时减少了巨噬细胞和T细胞的浸润以及促炎细胞因子和Toll样受体的表达[7]。Odanacatib（10mg/kg/day）经口给药处理胶原诱导的关节炎模型雌性DBA/1小鼠，从疾病诱导后第27天开始给药，持续21天。Odanacatib显著减少了骨和软骨降解的血清标志物（CTX I和CTX II）[8]。
| Cell experiment [1]: | |
Cell lines | Human renal carcinoma Caki, ACHN, and A498 cells; human cervical carcinoma Hela cells; human head and neck carcinoma AMC-HN4 cells |
Preparation Method | Cells were cultured in appropriate medium supplemented with 10% fetal bovine serum (FBS). Cells were treated with the Odanacatib (2µM) alone or in combination with a sub-lethal dose of anti-cancer drugs (e.g., TRAIL, doxorubicin, etoposide, 5-FU, cisplatin, oxaliplatin). |
Reaction Conditions | 2μM; 24h. |
Applications | Odanacatib alone had no significant effect on apoptosis, but Odanacatib markedly sensitized various human carcinoma cells to anti-cancer drug-induced apoptosis. Odanacatib treatment upregulated Bim protein expression via USP27x-mediated stabilization and induced down-regulation of Raptor, leading to increased mitochondrial ROS production. |
| Animal experiment [2]: | |
Animal models | 7- to 8-week-old male wild-type BALB/cJ mice |
Preparation Method | Mice were divided into normal and periapical disease groups. The disease was established by exposing and infecting the dental pulps of mandibular first molars with a polymicrobial mixture. Mice in the treatment group were administered Odanacatib (3.606mg/kg/week) orally, starting 1 week before disease induction and continuing until sample harvest at 7, 21, and 42 days post-infection. |
Dosage form | 3.606mg/kg/week; oral administration; once weekly for 6 weeks. |
Applications | Odanacatib treatment showed significant bone-protective effects in the periapical lesion area at different time points, as evidenced by X-ray and micro-CT analysis. Odanacatib dramatically decreased the infiltration of F4/80+ macrophages and CD3+ T cells in the lesion areas and reduced the levels of proinflammatory mRNAs (TNF-α, IL-6, IL-23α) and cytokines. |
| Cas No. | 603139-19-1 | SDF | |
| 别名 | 奥当卡替; MK-0822 | ||
| 化学名 | (2S)-N-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-[[(1S)-2,2,2-trifluoro-1-[4-(4-methylsulfonylphenyl)phenyl]ethyl]amino]pentanamide | ||
| Canonical SMILES | CC(C)(CC(C(=O)NC1(CC1)C#N)NC(C2=CC=C(C=C2)C3=CC=C(C=C3)S(=O)(=O)C)C(F)(F)F)F | ||
| 分子式 | C25H27F4N3O3S | 分子量 | 525.56 |
| 溶解度 | ≥ 17.7mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9027 mL | 9.5137 mL | 19.0273 mL |
| 5 mM | 380.5 μL | 1.9027 mL | 3.8055 mL |
| 10 mM | 190.3 μL | 951.4 μL | 1.9027 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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