DWK-1339 (MDR-1339)
(Synonyms: DWK-1339) 目录号 : GC31083
An inhibitor of amyloid-β aggregation
Cas No.:1018946-38-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | HT22 cells, a murine cell line of hippocampal origin, are grown in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum and 5% penicillin/streptomycin. At the outset, 90% confluent cells are dissociated and plated at 5 × 103 cells/well in a 96-well plate. When the cells are attached to the plate, the medium is replaced with plain DMEM. The cells are treated with MDR-1339. One hour after MDR-1339 treatment, 4 μL of pre-diluted 25 μM Aβ42 is added to the media, and the cells are further incubated for 18 h. For the determination of cell viability, 15 μL of 5 mg/mL MTT is added to each well and incubated for 3 h. The formazan that formed is dissolved in DMSO, and the absorbance is measured at 570-630 nm using a plate reader[1]. |
Animal experiment: | For this study, a total of 24 (n = 8 for each group) APP/PS1 [B6C3-Tg (APPswe, PSEN1dE9) 85Dbo/J] Tg mice are utilized. The mice are housed in a controlled environment under standard room temperature, relative humidity and a 12 h light/dark cycle with free access to food and water. APP/PS1 treated groups are orally administered with MDR-1339 at a dose of 30 or 100 mg/kg body weight once daily. MDR-1339 treatment is at the age of 29 weeks, and the treatment is conducted for 8 weeks[1]. |
References: [1]. Ha HJ, et al. Discovery of an Orally Bioavailable Benzofuran Analogue That Serves as a β-Amyloid Aggregation Inhibitor for the Potential Treatment of Alzheimer's Disease. J Med Chem. 2018 Jan 11;61(1):396-402. | |
DWK-1339 is an inhibitor of amyloid-β (Aβ) aggregation.1 It inhibits aggregation of monomeric Aβ (1-42) (Aβ42) and induces disaggregation of Aβ42 fibrils in vitro when used at concentrations ranging from 3.1 to 50 ?M. DWK-1339 (10 ?M) reduces Aβ42-induced toxicity in HT-22 cells. In vivo, DWK-1339 (10 mg/kg) increases step-through latency in a passive avoidance test and increases spontaneous alteration in the Y-maze compared with vehicle control mice in a mouse model of Aβ42-induced acute Alzheimer's disease. It also decreases brain levels of Aβ42 and increases spontaneous alteration in the Y-maze in the APP/PS1 transgenic mouse model of Alzheimer's disease.
1.Ha, H., Kang, D.W., Kim, H.-M., et al.Discovery of an orally bioavailable benzofuran analogue that serves as a β-amyloid aggregation inhibitor for the potential treatment of Alzheimer's diseaseJ. Med. Chem.61(1)396-402(2018)
| Cas No. | 1018946-38-7 | SDF | |
| 别名 | DWK-1339 | ||
| Canonical SMILES | COCCCC1=CC=C(OC(C2=CC=C(OC)C(OC)=C2)=C3)C3=C1 | ||
| 分子式 | C20H22O4 | 分子量 | 326.39 |
| 溶解度 | DMSO : ≥ 83.3 mg/mL (255.22 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 | 3.0638 mL | 15.3191 mL | 30.6382 mL |
| 5 mM | 0.6128 mL | 3.0638 mL | 6.1276 mL |
| 10 mM | 0.3064 mL | 1.5319 mL | 3.0638 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。
Identification of metabolites of MDR-1339, an inhibitor of β-amyloid protein aggregation, and kinetic characterization of the major metabolites in rats
We previously reported that MDR-1339, an inhibitor of β-amyloid protein aggregation, was likely to be eliminated by biotransformation in rats. The objective of this study was to determine the chemical identity of metabolites derived from this aggregate inhibitor and to characterize the kinetics of formation of these metabolites in rats. Using high performance liquid chromatography coupled with mass spectrometry with a hybrid triple quadrupole-linear ion trap, 7 metabolites and 1 potential metabolic intermediate were identified in RLM incubations containing MDR-1339. In addition to these, 3 glucuronide metabolites were detected in urine samples from rats receiving a 10 mg/kg oral dose of MDR-1339. When the kinetics of the formation of two major metabolites, M1 and M2, were analyzed assuming simple Michaelis-Menten kinetics, the Vmax and Km values were found to be 0.459 ± 0.0196 nmol/min/mg protein and 28.3 ± 3.07 μM for M1, and 0.101 ± 0.00537 nmol/min/mg protein and 14.7 ± 2.37 μM for M2, respectively. When chemically synthesized M1 and M2 were individually administered to rats intravenously at the dose of 5 mg/kg respectively, the volume of distribution and elimination clearance were determined to be 4590 ± 709 mL/kg and 68.4 ± 5.60 mL/min/kg for M1 and 15300 ± 8110 mL/kg and 98.0 ± 19.5 mL/min/kg for M2, respectively. When MDR-1339 was intravenously administered to rats at a dose of 5 mg/kg, the parent drug and M1 were readily detected for periods of up to 6 h after the administration, but M2 was observed only from 2 to 4 h. A standard moment analysis indicates that the formation clearance of M1 is 6.01 mL/min/kg, suggesting that 19.7% of the MDR-1339 dose was eliminated in rats. These observations indicate that the hepatic biotransformation of MDR-1339 results in the formation of at least 10 metabolites and that M1 is the major metabolite derived from this aggregation inhibitor in rats.
Discovery of an Orally Bioavailable Benzofuran Analogue That Serves as a β-Amyloid Aggregation Inhibitor for the Potential Treatment of Alzheimer's Disease
We developed an orally active and blood-brain-barrier-permeable benzofuran analogue (8, MDR-1339) with potent antiaggregation activity. Compound 8 restored cellular viability from Aβ-induced cytotoxicity but also improved the learning and memory function of AD model mice by reducing the Aβ aggregates in the brains. Given the high bioavailability and brain permeability demonstrated in our pharmacokinetic studies, 8 will provide a novel scaffold for an Aβ-aggregation inhibitor that may offer an alternative treatment for AD.