规格 | 价格 | 库存 | 数量 |
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10 mM * 1 mL in DMSO |
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1mg |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Other Sizes |
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靶点 |
GSK-3β (IC50 = 0.9 nM); PI3Kγ (IC50 = 282 nM)
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体外研究 (In Vitro) |
LY2090314 通过中断 ATP 结合来选择性抑制 GSK-3 的活性。 LY2090314具有保持β-catenin稳定的能力。作为单一疗法,LY2090314 的疗效有限。顺铂和卡铂与 LY3090314 联合使用时,在体外对实体瘤癌细胞系更有效。 [1]
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体内研究 (In Vivo) |
LY2090314 提高了顺铂和卡铂在实体瘤异种移植中的有效性。 [1]
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细胞实验 |
用不同浓度的药物处理细胞5小时。
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动物实验 |
Five million A375 human melanoma cancer cells are injected S.C. in the flank of female 6 to 8 week old athymic nude mice in a 1:1 mixture with matrigel. Tumors that can be felt are checked for daily in mice. When tumors are approximately 100 mm2 in size, mice are divided into groups and given LY2090314 (25 mg/kg Q3D) or a vehicle (20% Captisol/0.01N HCl) intravenously. Animal body weight and tumor volume (calculated using calipers) are recorded twice weekly. The formula used to determine tumor volumes is (a2 b)/2, where a represents the tumor's smaller dimension and b its larger dimension. LY2090314 is dosed at 2.5 mg/kg Q3D for combination studies with DTIC (60 mg/kg QD), and tumor growth is tracked.
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参考文献 |
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分子式 |
C28H25FN6O3
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分子量 |
512.5349
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精确质量 |
512.19722
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元素分析 |
C, 65.61; H, 4.92; F, 3.71; N, 16.40; O, 9.36
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CAS号 |
603288-22-8
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相关CAS号 |
603288-22-8
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外观&性状 |
Off-white to light yellow solid powder
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SMILES |
C1CCN(CC1)C(=O)N2CCN3C=C(C4=CC(=CC(=C43)C2)F)C5=C(C(=O)NC5=O)C6=CN=C7N6C=CC=C7
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InChi Key |
HRJWTAWVFDCTGO-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C28H25FN6O3/c29-18-12-17-15-34(28(38)32-7-3-1-4-8-32)11-10-33-16-20(19(13-18)25(17)33)23-24(27(37)31-26(23)36)21-14-30-22-6-2-5-9-35(21)22/h2,5-6,9,12-14,16H,1,3-4,7-8,10-11,15H2,(H,31,36,37)
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化学名 |
3-[6-fluoro-10-(piperidine-1-carbonyl)-1,10-diazatricyclo[6.4.1.04,13]trideca-2,4,6,8(13)-tetraen-3-yl]-4-imidazo[1,2-a]pyridin-3-ylpyrrole-2,5-dione
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别名 |
LY 2090314; LY2090314; LY-2090314
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HS Tariff Code |
2934.99.9001
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存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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溶解度 (体外) |
DMSO: ~100 mg/mL (~195.1 mM)
Water: <1 mg/mL Ethanol: ~2 mg/mL warmed (~3.9 mM) |
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溶解度 (体内) |
配方 1 中的溶解度: ≥ 1.25 mg/mL (2.44 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液。
例如,若需制备1 mL的工作液,可将100 μL 12.5 mg/mL澄清的DMSO储备液加入到400 μL PEG300中,混匀;再向上述溶液中加入50 μL Tween-80,混匀;然后加入450 μL生理盐水定容至1 mL。 *生理盐水的制备:将 0.9 g 氯化钠溶解在 100 mL ddH₂O中,得到澄清溶液。 配方 2 中的溶解度: ≥ 1.25 mg/mL (2.44 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液。 例如,若需制备1 mL的工作液,可将 100 μL 12.5 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中,混匀。 *20% SBE-β-CD 生理盐水溶液的制备(4°C,1 周):将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中,得到澄清溶液。 View More
配方 3 中的溶解度: 5% DMSO+45% PEG 300+ddH2O: 17mg/mL 配方 4 中的溶解度: 10 mg/mL (19.51 mM) in 20% HP-β-CD/10 mM citrate pH 2.0 (这些助溶剂从左到右依次添加,逐一添加), 悬浊液; 超声助溶。 1、请先配制澄清的储备液(如:用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液,按从左到右的顺序依次添加助溶剂,澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明,并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀/澄清;向上述体系中加入50 μL Tween-80,混合均匀/澄清;然后继续加入450 μL ddH2O (或 saline)定容至 1 mL; 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出,可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果,工作液请现配现用! 6、如不确定怎么将母液配置成体内动物实验的工作液,请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
制备储备液 | 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 |
1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;
3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);
4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。
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)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。
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 ddH2O,混匀澄清。
(1) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
(2) 一定要按顺序加入溶剂 (助溶剂) 。
NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT01287520 | Completed | Drug: LY2090314 Drug: pemetrexed |
Advanced Cancer | Eli Lilly and Company | November 2007 | Phase 1 |
NCT01214603 | Completed | Drug: LY2090314 | Leukemia | Eli Lilly and Company | November 2010 | Phase 2 |
LY2090314 is a GSK inhibitor which elevated Wnt signaling in melanoma cell lines. td> |
LY2090314 potently induces apoptotic cell death in a range of melanoma cell lines irrespective of BRAF mutation status. td> |
Cell death induced by LY2090314 is dependent on β-catenin and GSK3β knockdown increases the sensitivity of cells to LY2090314.A. Melanoma cells stably transfected with shRNAs targeting β-catenin display decreased β-catenin and Axin2 protein expression by western blot. A375 (B) and M14 (C) cells expressing shRNAs targeting β-catenin (● Control; ■ β-catenin shRNA 1;▲β-catenin shRNA 2; ▼ β-catenin shRNA 3) become resistant to LY2090314 suggesting that β-catenin is required for apoptotic cell death in response to LY2090314.D, E.A375 cells targeted with GSK3β shRNA, but not GSK3α shRNA, demonstrates increased sensitivity to LY2090314 (4.5nM, 72hr).PLoS One.2015 Apr 27;10(4):e0125028. td> |
LY2090314 demonstrates activity in cell lines resistant to the BRAF inhibitor Vemurafenib and has an independent mechanism of action.PLoS One.2015 Apr 27;10(4):e0125028. td> |
LY2090314 elevates Axin2 gene expression in vivo, demonstrates single agent activity in the A375 xenograft model of melanoma and enhances the efficacy of DTIC.PLoS One.2015 Apr 27;10(4):e0125028. td> |