Zotarolimus(ABT-578)
(Synonyms: 佐他莫司; ABT-578; A 179578) 目录号 : GC14224
Zotarolimus(ABT-578)是一种免疫抑制剂，可通过抑制亲免疫蛋白FKBP12的结合发挥作用，IC50值为2.8±0.16nM。
Cas No.:221877-54-9
Sample solution is provided at 25 µL, 10mM.
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Zotarolimus(ABT-578) is an immunosuppressant that inhibits immunophilin FKBP12 binding with an IC50 of 2.8±0.16nM[1]. Zotarolimus binds to the immunoaffinity protein FKBP12 to form the Zotarolimus-FKBP12 complex, which inhibits mammalian target of rapamycin (mTOR) to regulate intracellular metabolism[2]. Zotarolimus has been widely used in the development of novel drug-eluting stents to prevent coronary restenosis[3].
In vitro, Zotarolimus treatment for 48h inhibited human coronary artery smooth muscle cell (HCASMC) proliferation, with an IC50 value of 0.8nM[4]. Treatment with 1µM Zotarolimus for 48 hours significantly inhibited the migration of human coronary artery endothelial cells (HCAECs) and reduced the expression of pro-inflammatory cytokines[5].
In vivo, Zotarolimus treatment via intraperitoneal injection at a dose of 2mg/kg/day for 3 weeks suppressed tumor growth in the HCT-116 cell xenograft tumor mouse model[6]. Combined administration of Zotarolimus (2mg/kg/day) and 5-fluorouracil (100mg/kg/week) by intraperitoneal injection for 3 weeks significantly inhibited the progression of lung adenocarcinoma in the A549 cell xenograft mouse model and suppressed the expression of IL-1β and TNF-α[7].
References:
[1] Garcia-Touchard A, Burke S E, Toner J L, et al. Zotarolimus-eluting stents reduce experimental coronary artery neointimal hyperplasia after 4 weeks[J]. European heart journal, 2006, 27(8): 988-993.
[2] Shokati T, Drake S H, Zhao W, et al. Structural Identification of Zotarolimus (ABT-578) Metabolites Generated by Human Liver Microsomes Using Ion-Trap and High-Resolution Time-of-Flight Mass Spectrometry in Combination with the Analysis of Fragmentation Patterns[J]. Metabolites, 2023, 13(10): 1093.
[3] Burke S E, Kuntz R E, Schwartz L B. Zotarolimus (ABT-578) eluting stents[J]. Advanced drug delivery reviews, 2006, 58(3): 437-446.
[4] Chen Y W, Smith M L, Sheets M, et al. Zotarolimus, a novel sirolimus analogue with potent anti-proliferative activity on coronary smooth muscle cells and reduced potential for systemic immunosuppression[J]. Journal of cardiovascular pharmacology, 2007, 49(4): 228-235.
[5] Steinfeld D S, Liu A P, Hsu S H, et al. Comparative assessment of transient exposure of paclitaxel or zotarolimus on in vitro vascular cell death, proliferation, migration, and proinflammatory biomarker expression[J]. Journal of Cardiovascular Pharmacology, 2012, 60(2): 179-186.
[6] Chang G R, Kuo C Y, Tsai M Y, et al. Anti-cancer effects of zotarolimus combined with 5-fluorouracil treatment in HCT-116 colorectal cancer-bearing BALB/c nude mice[J]. Molecules, 2021, 26(15): 4683.
[7] Wu C F, Wu C Y, Chiou R Y Y, et al. The anti-cancer effects of a zotarolimus and 5-fluorouracil combination treatment on A549 cell-derived tumors in Balb/c nude mice[J]. International Journal of Molecular Sciences, 2021, 22(9): 4562.
Zotarolimus(ABT-578)是一种免疫抑制剂，可通过抑制亲免疫蛋白FKBP12的结合发挥作用，IC50值为2.8±0.16nM[1]。Zotarolimus与FKBP12结合形成Zotarolimus-FKBP12复合物后，能够抑制哺乳动物雷帕霉素靶蛋白（mTOR），从而调控细胞内代谢过程[2]。Zotarolimus已广泛应用于新型药物洗脱支架的研发，用于预防冠状动脉再狭窄[3]。
在体外，Zotarolimus处理48小时可抑制人冠状动脉平滑肌细胞(HCASMC)的增殖，IC50值为0.8nM[4]。使用1µM的Zotarolimus处理人冠状动脉内皮细胞(HCAECs) 48小时，能显著抑制细胞迁移并降低促炎细胞因子的表达[6]。
在体内，每日腹腔注射2mg/kg/day剂量的Zotarolimus连续3周，可抑制HCT-116细胞移植瘤小鼠模型的肿瘤生长[6]。联合使用Zotarolimus（2mg/kg/day）与5-氟尿嘧啶（100mg/kg/week）腹腔注射治疗3周，能显著抑制A549细胞移植瘤模型中肺腺癌的进展，并降低IL-1β和TNF-α的表达水平[7]。
| Cell experiment [1]: | |
Cell lines | Human coronary artery smooth muscle cell (HCASMC) |
Preparation Method | HCASMCs were cultured in SmGM-2 growth media, containing fetal bovine serum (5%) and a specific cocktail of growth factors and antibiotics. All cells were cultured in a 37ºC and 5% CO2 environment, and refed every 3–4 days or passed on reaching 80% confluence. HCASMCs were seeded at a density optimal for growth (1.5×104 cells per centimeter square) in black-walled 96-well plates. Proliferation of HCASMCs under constant exposure to Zotarolimus over a range of concentrations (0.00001, 0.0001, 0.001, 0.01, 0.1, and 1µM) and over a period of 48 hours was observed using the pico green dye assay used for evaluation. |
Reaction Conditions | 0.00001, 0.0001, 0.001, 0.01, 0.1, and 1µM; 48h |
Applications | Zotarolimus treatment significantly reduced the viability of HCASMCs in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Male BALB/c nude mice |
Preparation Method | Six weeks old male BALB/c nude mice were maintained in a constant temperature (22±2°C) and constant humidity (55±5%) environment with a light/dark cycle of 12h/12h. After the mice were anesthetized by intraperitoneal injection of Zoletil, 100µl HCT-116 cell suspension containing 1×106 live HCT-116 cells was injected subcutaneously into the hind limbs. After 7 days of continuous feeding, the mice with tumors of 4-5mm in diameter were divided into 3 groups. Tumor growth was analyzed after three weeks of intraperitoneal injection of 5-fluorouracil (5-FU; 50mg/kg/week) and Zotarolimus (2mg/kg/day) in the second and third groups, respectively. After three weeks, tumor growth was analyzed. |
Dosage form | 2mg/kg/day for 3 weeks; i.p. |
Applications | Zotarolimus treatment suppressed tumor growth in HCT-116 cell xenograft tumor mouse model. |
References: | |
| Cas No. | 221877-54-9 | SDF | |
| 别名 | 佐他莫司; ABT-578; A 179578 | ||
| 分子式 | C52H79N5O12 | 分子量 | 966.21 |
| 溶解度 | DMF: 15mg/mL,DMSO: 15mg/mL,Ethanol: 20mg/mL,Ethanol:PBS (pH 7.2) (1:3): 0.25mg/mL | 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 | 1.035 mL | 5.1749 mL | 10.3497 mL |
| 5 mM | 207 μL | 1.035 mL | 2.0699 mL |
| 10 mM | 103.5 μL | 517.5 μL | 1.035 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
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