LY2886721
(Synonyms: N-[3-[(4AS,7AS)-2-氨基-4A,5-二氢-4H-呋喃并[3,4-D][1,3]噻嗪-7A(7H)-基]-4-氟苯基]-5-氟-2-吡啶甲酰胺) 目录号 : GC17227
An inhibitor of BACE
Cas No.:1262036-50-9
Sample solution is provided at 25 µL, 10mM.
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LY2886721 is an oral and furothiazine-based inhibitor of β site-amyloid protein cleaving enzyme (BACE) with IC50 of 20.3nM. This product has the potency for the treatment of Alzheimer's disease.
BACE, also known as Beta-Secretase 1, is an aspartic-acid protease that plays important role in the formation of myelin sheaths in peripheral nerve cells.
In vitro, treatment of LY2886721 leads to the inhibition of Aβ in HEK293Swe with IC50 of 18.7nM and PDAPP neuronal culture with IC50 10.7 nM1. LY2886721 decreases CSF sAPPβ and increases CSF sAPPα in a dose- dependent manner 2.
In PDAPP mice, oral administration of LY2886721 resulted in a reduction in brain Aβ, C99 and sAPPβ in a dose-dependent pattern 2. Aβ levels in the brain were decreased by 20% -65% as compared with the vehicle-treated groups 3 hours after treatment of LY2886721 at a dosage of 3-30 mg/kg per mice. In addition, LY2886721 significantly lowers plasma and CSF Aβs in the MAD study 1.
References:
1. Vassar R. BACE1 inhibitor drugs in clinical trials for Alzheimer's disease. Alzheimer's research & therapy. 2014;6(9):89.
2. Nishitomi K, Sakaguchi G, Horikoshi Y, et al. BACE1 inhibition reduces endogenous Abeta and alters APP processing in wild-type mice. Journal of neurochemistry. 2006;99(6):1555-1563.
| Animal experiment [1]: | |
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Animal models |
PDAPP mice |
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Dosage form |
3, 10 or 30 mg/kg; p.o. |
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Applications |
At all 3 doses, LY2886721 significantly reduced hippocampal and cortical levels of Aβ1-x. In addition, LY2886721 significantly lowered brain parenchymal levels of C99 and sAPPβ. Although cortical levels of C99 were reduced significantly by LY2886721 at the doses of 10 and 30 mg/kg, the effect of LY2886721 at the dose of 3 mg/kg failed to reach statistical significance. On the other hand, the sAPPβ levels were significantly decreased by LY2886721 at all 3 doses. |
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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]. May PC, Willis BA, Lowe SL, Dean RA, Monk SA, Cocke PJ, Audia JE, Boggs LN, Borders AR, Brier RA, Calligaro DO, Day TA, Ereshefsky L, Erickson JA, Gevorkyan H, Gonzales CR, James DE, Jhee SS, Komjathy SF, Li L, Lindstrom TD, Mathes BM, Martényi F, Sheehan SM, Stout SL, Timm DE, Vaught GM, Watson BM, Winneroski LL, Yang Z, Mergott DJ. The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans. J Neurosci. 2015 Jan 21;35(3):1199-210. | |
| Cas No. | 1262036-50-9 | SDF | |
| 别名 | N-[3-[(4AS,7AS)-2-氨基-4A,5-二氢-4H-呋喃并[3,4-D][1,3]噻嗪-7A(7H)-基]-4-氟苯基]-5-氟-2-吡啶甲酰胺 | ||
| 化学名 | N-[3-[(4aS,7aS)-2-amino-4,4a,5,7-tetrahydrofuro[3,4-d][1,3]thiazin-7a-yl]-4-fluorophenyl]-5-fluoropyridine-2-carboxamide | ||
| Canonical SMILES | C1C2CSC(=NC2(CO1)C3=C(C=CC(=C3)NC(=O)C4=NC=C(C=C4)F)F)N | ||
| 分子式 | C18H16F2N4O2S | 分子量 | 390.41 |
| 溶解度 | ≥ 19.52mg/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 | 2.5614 mL | 12.807 mL | 25.6141 mL |
| 5 mM | 0.5123 mL | 2.5614 mL | 5.1228 mL |
| 10 mM | 0.2561 mL | 1.2807 mL | 2.5614 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet