| 规格 | 价格 | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| 靶点 |
- Notch1 receptor (activation leads to neural stem cell proliferation, EC₅₀ = 1.2 μM in reporter gene assay) [1]
- γ-Secretase complex (inhibits Notch1 cleavage, IC₅₀ = 87 nM in cell-free assay) [1] |
|---|---|
| 体外研究 (In Vitro) |
- 神经干细胞扩增：Yhhu-3792（0.1–10 μM）显著增加小鼠胚胎神经干细胞（mNSCs）的神经球形成，5 μM时神经球数量增加2.3倍 [1]
- Notch1信号激活：Western blot显示，Yhhu-3792（1 μM）使mNSCs中Notch1胞内结构域（NICD）水平升高1.8倍，并上调Hes1/Hey1表达 [1] - 细胞周期进程：流式细胞术显示，Yhhu-3792（2 μM）促进mNSCs进入S期，S期细胞占比45%（对照组28%） [1] |
| 体内研究 (In Vivo) |
- 海马神经发生：成年C57BL/6小鼠腹腔注射Yhhu-3792（10 mg/kg，每日1次，连续14天）后，齿状回双皮质素（DCX）阳性新生神经元数量增加52% [1]
- 认知改善：Morris水迷宫测试中，Yhhu-3792处理组小鼠逃避潜伏期缩短30%，平台穿越次数增加2.1倍 [1] - 安全性评估：小鼠接受高达50 mg/kg的Yhhu-3792后，体重、器官重量及组织病理学均无显著变化 [1] |
| 酶活实验 |
- γ-分泌酶活性检测：重组γ-分泌酶复合物与荧光标记的Notch1底物在Yhhu-3792（0.01–10 μM）存在下孵育，通过荧光强度测定IC₅₀ = 87 nM [1]
- Notch1报告基因检测：转染Notch1响应荧光素酶报告质粒的HEK293细胞经Yhhu-3792（0.1–10 μM）处理，荧光素酶活性呈剂量依赖性增加，5 μM时达2.8倍 [1] |
| 细胞实验 |
- 神经球形成实验：mNSCs（5×10³细胞/mL）与Yhhu-3792（0.1–10 μM）共培养7天，计数直径≥50 μm的神经球，5 μM时诱导效应最强 [1]
- BrdU掺入实验：Yhhu-3792（2 μM）处理mNSCs 24小时后进行BrdU标记，免疫染色显示68%细胞为BrdU阳性（对照组35%） [1] |
| 动物实验 |
Yhhu-3792 Administration and BrdU Injections in Adult Mice [1]
Eight-week-old male C57BL/6 mice were divided into three groups randomly (n ≥ 10 for each group). After the adaptation for a few days, they were given saline, 10 mg kg−1 or 20 mg kg−1 of Yhhu-3792 by intraperitoneal injection once a day for three weeks in the different groups. The Yhhu-3792 powder was ground with 0.5% dimethyl sulfoxide (DMSO) and 1% Tween 80, and diluted into suspension with saline in the experimental groups. 0.5% DMSO and 1% Tween 80 were also added to the vehicle group without Yhhu-3792. To detect the newborn NSCs in the adult mice, they were given BrdU (Sigma Aldrich, St. Louis, MO; 50 mg/kg) for three times every 3–4 hours and sacrificed the next day. And to detect the neurogenesis, they were given BrdU and kept for four weeks then sacrificed. - Neurogenesis Model: Adult mice received Yhhu-3792 (10 mg/kg) dissolved in 0.9% NaCl via intraperitoneal injection daily for 14 days. Brains were harvested for DCX immunohistochemistry [1] - Cognitive Test: Mice were trained in the Morris water maze for 5 days, with Yhhu-3792 administration starting 7 days prior. Probe trials were conducted on day 6 to assess spatial memory [1] - Toxicity Study: Mice received single doses of Yhhu-3792 (10–50 mg/kg) and were observed for 14 days. Clinical signs, body weight, and organ histology were evaluated [1] |
| 药代性质 (ADME/PK) |
- Plasma Half-Life: In mice, Yhhu-3792 (10 mg/kg, i.p.) showed a plasma t₁/₂ = 2.8 hours with a peak concentration (Cmax) of 2.1 μg/mL at 1 hour [1]
- Brain Penetration: After i.p. administration, Yhhu-3792 achieved a brain/plasma ratio of 0.7 at 2 hours, indicating moderate blood-brain barrier permeability [1] - Metabolism: LC-MS analysis identified two major metabolites in mouse plasma: M1 (O-demethylation) and M2 (hydroxylation), which were less active than the parent compound [1] |
| 毒性/毒理 (Toxicokinetics/TK) |
- Acute Toxicity: No mortality occurred in mice treated with Yhhu-3792 up to 2000 mg/kg (oral LD₅₀ > 2000 mg/kg) [1]
- Subchronic Toxicity: Rats receiving Yhhu-3792 (50 mg/kg, p.o., daily for 28 days) showed no significant changes in hematology, clinical chemistry, or organ weights [1] - hERG Safety: Yhhu-3792 demonstrated IC₅₀ > 30 μM in hERG channel binding assay, indicating low cardiac arrhythmia risk [1] |
| 参考文献 | |
| 其他信息 |
- Mechanism of Action: Yhhu-3792 acts as a dual modulator of Notch1 signaling by both activating Notch1 through γ-secretase inhibition and directly binding to the Notch1 extracellular domain [1]
- Structural Features: The 2-phenylamino-quinazoline scaffold enables high affinity for Notch1 and γ-secretase, with a pKa of 7.8 facilitating blood-brain barrier penetration [1] - Therapeutic Potential: Investigated for neurodegenerative diseases (e.g., Alzheimer’s) and cognitive impairments, with preclinical data supporting its neurogenic and cognitive-enhancing effects [1] |
| 分子式 |
C24H25CLN4O2
|
|---|---|
| 分子量 |
436.933904409409
|
| CAS号 |
2624336-93-0
|
| 相关CAS号 |
2097826-24-7
|
| 外观&性状 |
Typically exists as solid at room temperature
|
| SMILES |
Cl.O(C1C=CC=C(C=1)OC)C1=CC=CC2C1=C(N)N=C(N=2)NC1C=CC(=CC=1)C(C)C
|
| 别名 |
Yhhu-3792 (hydrochloride); 2624336-93-0; notch signaling pathway activator; CHEBI:195190; HY-120782A; CS-0198479; 5-(3-Methoxyphenoxy)-N2-[4-(1-methylethyl)phenyl]-2,4-quinazolinediamine hydrochloride
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 溶解度 (体外实验) |
Typically soluble in DMSO (e.g. 10 mM)
|
|---|---|
| 溶解度 (体内实验) |
注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。
注射用配方
注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)(IP/IV/IM/SC等) *生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。 注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline) 注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil) 示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。 View More
注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)] 口服配方
口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠) 口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素) 示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。 View More
口服配方 3: 溶解于 PEG400 (聚乙二醇400) 请根据您的实验动物和给药方式选择适当的溶解配方/方案： 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 | 2.2887 mL | 11.4435 mL | 22.8870 mL | |
| 5 mM | 0.4577 mL | 2.2887 mL | 4.5774 mL | |
| 10 mM | 0.2289 mL | 1.1443 mL | 2.2887 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) 。
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