Emixustat (ACU-4429)
(Synonyms: ACU-4429) 目录号 : GC31373
Emixustat(ACU-4429)是一种抑制异构酶复合物的小分子视觉周期调节剂。
Cas No.:1141777-14-1
Sample solution is provided at 25 µL, 10mM.
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Emixustat(ACU-4429) is a first in class small-molecule visual cycle modulator that inhibits the isomerase complex. As an inhibitor of visual cycle isomerase, the IC50 value is 4.4 nM[1].
Emixustat strongly inhibits 11-cis-retinol production with an IC50 value of 232±3 nM[2]. A concentration-dependent reduction of 11-cis-ROL production (i.e., inhibition of RPE65 isomerase activity) by emixustat(10-5 to 10-10 M)[1].
Emixustat(0.01-3.0 mg/kg; p.o) was found to reduce the production of visual chromophore (11-cis retinal) in wild-type mice following a single oral dose (ED50 = 0.18 mg/kg) [1]. In 40 subjects (mean age, 38 years) Emixustat (n = 30) (5, 10, 20, 30, or 40 mg; 14-day) was rapidly absorbed (median T(max), 3.0-5 hours) and readily eliminated (mean t(1/2), 4.6-7.9 hours), and mean C(max) generally increased in proportion to dose. Systemic adverse events were minimal[3]. Emixustat significantly abates permeability after Ischemia Reperfusion(IR) on vascular permeability in mice[4].
References:
[1]. Bavik C, Henry SH, et,al.Visual Cycle Modulation as an Approach toward Preservation of Retinal Integrity. PLoS One. 2015 May 13;10(5):e0124940. doi: 10.1371/journal.pone.0124940. PMID: 25970164; PMCID: PMC4430241.
[2]. Kiser PD, Zhang J, et,al.Catalytic mechanism of a retinoid isomerase essential for vertebrate vision. Nat Chem Biol. 2015 Jun;11(6):409-15. doi: 10.1038/nchembio.1799. Epub 2015 Apr 20. PMID: 25894083; PMCID: PMC4433804.
[3].Kubota R, Al-Fayoumi S, et,al. Phase 1, dose-ranging study of emixustat hydrochloride (ACU-4429), a novel visual cycle modulator, in healthy volunteers. Retina. 2014 Mar;34(3):603-9. doi: 10.1097/01.iae.0000434565.80060.f8. PMID: 24056528.
[4].Dreffs A, Lin CM, et,al. All-trans-Retinaldehyde Contributes to Retinal Vascular Permeability in Ischemia Reperfusion. Invest Ophthalmol Vis Sci. 2020 Jun 3;61(6):8. doi: 10.1167/iovs.61.6.8. PMID: 32492112; PMCID: PMC7415894.
Emixustat(ACU-4429)是一种抑制异构酶复合物的小分子视觉周期调节剂。作为视循环异构酶抑制剂,IC50值为4.4 nM[1]。
Emixustat抑制11-顺式视黄醇的产生,IC50值为232±3 nM[2]。Emixustat (10-5 ~ 10-10 M) 以浓度依赖性降低11-cis-ROL的产量 (即抑制RPE65异构酶活性) [1]。
研究发现,单次口服Emixustat (0.01-3.0 mg/kg; p.o)可减少野生型小鼠视觉发色团(11-cis retinal)的产生(ED50 = 0.18 mg/kg)[1]。40名受试者(平均年龄38岁)。Emixustat (n = 30)(5-40 mg;14days)吸收迅速(中位值3.0-5小时),容易消除(平均时间4.6-7.9小时),平均峰浓度随剂量成比例增加。不良事件极少[3]。Emixustat显著降低小鼠缺血再灌注后血管通透性[4]。
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Animal experiment [1]: |
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Animal models |
BALB/c mice (8 weeks) |
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Preparation method |
Dark-adapted (12 hours) BALB/c mice (8 weeks, n = 4/group) were orally dosed with emixustat (0.01-3.0 mg/kg) or vehicle (water). At 4 hours post-dose, animals were photobleached (5000 lux white light, 10 min) without anesthesia or mydriatics, returned to the dark for 2 hours, and then euthanized under red light. |
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Dosage form |
0.01-3.0 mg/kg; p.o |
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Applications |
Emixustat was found to reduce the production of visual chromophore (11-cis retinal) in wild-type mice following a single oral dose (ED50 = 0.18 mg/kg). |
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References: [1]. Bavik C, Henry SH,et,al. Visual Cycle Modulation as an Approach toward Preservation of Retinal Integrity. PLoS One. 2015 May 13;10(5):e0124940. doi: 10.1371/journal.pone.0124940. PMID: 25970164; PMCID: PMC4430241. |
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| Cas No. | 1141777-14-1 | SDF | |
| 别名 | ACU-4429 | ||
| Canonical SMILES | O[C@H](CCN)C1=CC(OCC2CCCCC2)=CC=C1 | ||
| 分子式 | C16H25NO2 | 分子量 | 263.38 |
| 溶解度 | DMSO : ≥ 43 mg/mL (163.26 mM) | 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 | 3.7968 mL | 18.984 mL | 37.968 mL |
| 5 mM | 0.7594 mL | 3.7968 mL | 7.5936 mL |
| 10 mM | 0.3797 mL | 1.8984 mL | 3.7968 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: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet