LY2090314
(Synonyms: LY 2090314;LY-2090314) 目录号 : GC17187
A potent and selective inhibitor of GSK3
Cas No.:603288-22-8
Sample solution is provided at 25 µL, 10mM.
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IC50: 1.5 nM (GSK-3α); 0.9 nM (GSK-3β)
LY2090314 (LY) is a potent inhibitor of glycogen synthase kinase-3 (GSK-3) which plays an important role in various pathways, such as protein synthesis initiation, cell proliferation/differentiation, and apoptosis.
In vitro: LY2090314 selectively inhibits the activity of GSK-3 by inhibiting ATP binding. LY2090314 was reported to be able to stabilize β-catenin. As monotherapy, LY2090314 aslso showed limited efficacy. In solid tumor cancer cell lines, LY3090314 was found to enhance the efficacy of cisplatin and carboplatin [1].
In vivo: Even in Mdr1a-, Bcrp-, and Mrp2-knockout rats, the metabolites of LY2090314 did not appear in systemic circulation, and the urinary excretion was not found to be enhanced, since the hypothesized impaired biliary excretion of metabolites in the absence of these canalicular transporters was not observed. Dog metabolite disposition was similar, with the exception of LY2090314 glucuronide. Moreover, LY2090314 enhances the efficacy of cisplatin and carboplatin in solid tumor cancer xenografts [1]
Clinical trial: In advanced solid tumor patients (pts), LY2090314 (LY) was dosed intravenously as a lead-in 7 days prior to the first administration of the triplet combination with PC. Preliminary pharmacokinetic analyses showed that exposure increased as dose increased over the dose range studied with a short terminal elimination half-life calculated in the majority of patients. Large number of pretreated patients that experienced stable disease suggests continued evaluation of LY in NSCLC may be warranted.
Reference:
[1] Brail LH, et al. J Clin Oncol, 2011, 29, abstr 3030.
| Cell experiment [1]: | |
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Cell lines |
A panel of melanoma cell lines |
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Preparation method |
Soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
20 nM |
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Applications |
LY2090314 potently induced apoptotic cell death in a panel of melanoma cell lines irrespective of BRAF mutation status. LY2090314 (20 nM) promoted a time-dependent stabilization of β-catenin total protein as well as an induction of Axin2. LY2090314 was highly selective towards GSK3 as demonstrated by its fold selectivity relative to a large panel of kinases. Cell death induced by LY2090314 was dependent on β-catenin and GSK3β knockdown increased the sensitivity of cells to LY2090314. LY2090314 was active in cell lines resistant to Vemurafenib and showed an independent mechanism of action. |
| Animal experiment [1, 2]: | |
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Animal models |
Athymic nude mice bearing A375 melanoma xenografts |
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Dosage form |
Intravenous injection, 25 mg/kg, every 3 days |
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Application |
LY2090314 (25 mg/kg Q3D, i.v.) elevated Axin2 gene expression in vivo, demonstrated single agent activity in the A375 xenograft model of melanoma and enhanced the efficacy of DTIC. LY2090314 exhibited high clearance (approximating hepatic blood flow) and a moderate volume of distribution (appr 1-2 L/kg) resulting in rapid elimination (half-life appr 0.4, 0.7, and 1.8-3.4 hours in rats, dogs, and humans, respectively). LY2090314 was rapidly cleared by extensive metabolism with negligible circulating metabolite exposures due to biliary excretion of metabolites into feces with no apparent intestinal reabsorption. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Atkinson J M, Rank K B, Zeng Y, et al. Activating the Wnt/β-catenin pathway for the treatment of melanoma–application of ly2090314, a novel selective inhibitor of glycogen synthase kinase-3[J]. PLoS One, 2015, 10(4): e0125028. [2]. Zamek-Gliszczynski MJ, et al. Pharmacokinetics, metabolism, and excretion of the glycogen synthase kinase-3 inhibitor LY2090314 in rats, dogs, and humans: a case study in rapid clearance by extensive metabolism with low circulating metabolite exposure. Dr |
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| Cas No. | 603288-22-8 | SDF | |
| 别名 | LY 2090314;LY-2090314 | ||
| 化学名 | 3-(9-fluoro-2-(piperidine-1-carbonyl)-1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-7-yl)-4-(imidazo[1,2-a]pyridin-3-yl)-1H-pyrrole-2,5-dione | ||
| Canonical SMILES | FC1=C([H])C2=C(C(C(C(C(N([H])C3=O)=O)=C3C4=C([H])N=C5N4C([H])=C([H])C([H])=C5[H])=C6[H])=C1[H])N6C([H])([H])C([H])([H])N(C(N7C([H])([H])C([H])([H])C([H])([H])C([H])([H])C7([H])[H])=O)C2([H])[H] | ||
| 分子式 | C28H25FN6O3 | 分子量 | 512.53 |
| 溶解度 | ≥ 91 mg/mL in DMSO, ≥ 4.27 mg/mL in EtOH with ultrasonic and warming | 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 | 1.9511 mL | 9.7555 mL | 19.5111 mL |
| 5 mM | 0.3902 mL | 1.9511 mL | 3.9022 mL |
| 10 mM | 0.1951 mL | 0.9756 mL | 1.9511 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。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet