YO-01027 (Dibenzazepine, DBZ)
(Synonyms: 二苯并氮卓,gamma-Secretase Inhibitor XX,YO01027) 目录号 : GC17671
YO-01027 (Dibenzazepine, DBZ)是一种γ-分泌酶抑制剂，对APP裂解和Notch裂解的IC50值分别为2.64±0.30nM和2.92±0.22nM。
Cas No.:209984-56-5
Sample solution is provided at 25 µL, 10mM.
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YO-01027 (Dibenzazepine, DBZ) is a γ-secretase inhibitor, with the IC50 values of 2.64±0.30 and 2.92±0.22nM for APPL and Notch cleavage, respectively[1]. YO-01027 has the potential to modulate Notch-induced oncogenic events, inhibiting multiple tumor growth[2]. YO-01027 has been widely used as a model compound for the development of a range of multifunctional molecular probes targeting signal peptidases [3].
In vitro, YO-01027 treatment for 24h inhibited B16 cells, with an IC50 value of 300μM [4]. YO-01027 treatment for 48 hours significantly inhibited the viral replication in dengue virus (DENV)-infected Huh7.5.1 cells with an EC50 value of 20nM[5]. YO-01027 treatment at 0.2μM for 7 days significantly reduced cell viability and survival of ALL-SIL cells [6].
In vivo, YO-01027 treatment via intraperitoneal injection at a dose of 5µmol/kg/day for 14 days ameliorated liver steatosis in CoreTg mice and reduced expression of SREBP-1c without affecting body weight[7]. Intraperitoneal injection of YO-01027 (250μg/100g/day) for 8 days improved renal fibrosis in mice with unilateral ureteral ligation (UUO) injury, reduced collagen deposition and fibrosis marker expression in renal tissue[8].
References:
[1] Groth C, Alvord W G, Quinones O A, et al. Pharmacological analysis of Drosophila melanogaster γ-secretase with respect to differential proteolysis of Notch and APP[J]. Molecular pharmacology, 2010, 77(4): 567-574.
[2] Usui T, Sakurai M, Umata K, et al. Hedgehog signals mediate anti-cancer drug resistance in three-dimensional primary colorectal cancer organoid culture[J]. International journal of molecular sciences, 2018, 19(4): 1098.
[3] Fuwa H, Takahashi Y, Konno Y, et al. Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic γ-secretase inhibitors[J]. ACS chemical biology, 2007, 2(6): 408-418.
[4] Li Y, Zhang C, Nie Y, et al. Antitumor Activity of Ethyl Acetate Extraction of Wikstroemia chamaedaphne: Cell Cycle Arrest and Apoptosis-Inducing Activity in Melanoma Cells[J]. Records of Natural Products, 2022, 16(6): 571.
[5] Qiao W, Xie X, Shi P Y, et al. Druggable genome screens identify SPP as an antiviral host target for multiple flaviviruses[J]. Proceedings of the National Academy of Sciences, 2025, 122(8): e2421573122.
[6] Hounjet J, Habets R, Schaaf M B, et al. The anti-malarial drug chloroquine sensitizes oncogenic NOTCH1 driven human T-ALL to γ-secretase inhibition[J]. Oncogene, 2019, 38(27): 5457-5468.
[7] Hirano J, Okamoto T, Sugiyama Y, et al. Characterization of SPP inhibitors suppressing propagation of HCV and protozoa[J]. Proceedings of the National Academy of Sciences, 2017, 114(50): E10782-E10791.
[8] Xiao Z, Zhang J, Peng X, et al. The Notch γ-secretase inhibitor ameliorates kidney fibrosis via inhibition of TGF-β/Smad2/3 signaling pathway activation[J]. The international journal of biochemistry & cell biology, 2014, 55: 65-71.
YO-01027 (Dibenzazepine, DBZ)是一种γ-分泌酶抑制剂，对APP裂解和Notch裂解的IC50值分别为2.64±0.30nM和2.92±0.22nM[1]。YO-01027具有调节Notch诱导的致癌事件、抑制多种肿瘤生长的潜力[2]。YO-01027已作为靶向信号肽酶的多功能分子探针开发的模型化合物[3]。
在体外，YO-01027处理24小时可抑制B16细胞活性，IC50值为300μM[4]。YO-01027处理登革病毒（DENV）感染的Huh7.5.1细胞48小时能显著抑制病毒复制，EC50值为20nM[5]。0.2μM的YO-01027处理ALL-SIL细胞7天可显著降低细胞活力和存活率[6]。
在体内，CoreTg小鼠每日腹腔注射YO-01027（5µmol/kg/day；持续14天）可改善肝脏脂肪变性并降低SREBP-1c表达，且不影响体重[7]。单侧输尿管结扎（UUO）损伤小鼠每日腹腔注射YO-01027（250μg/100g/day；持续8天）能改善肾纤维化，减少肾组织胶原沉积和纤维化标志物表达[8]。
| Cell experiment [1]: | |
Cell lines | ALL-SIL cells |
Preparation Method | ALL-SIL cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS), 2mM GlutaMAX, and 50U/ml penicillin/streptomycin. Cells were treated with dimethyl sulfoxide (DMSO), 0.2µM YO-01027, and 1µM DAPT on day 0. Cell viability and proliferation assays were performed on day 7. |
Reaction Conditions | 0.2µM; 7 days |
Applications | YO-01027 treatment significantly reduced the number of living ALL-SIL cells and reduced both cell viability and proliferation. |
| Animal experiment [2]: | |
Animal models | CoreTg mice |
Preparation Method | CoreTg mice were maintained at room temperature (23±2°C) under a 12-h light/dark cycle (lights on at 8:00 am). Vehicle or 5µmol/kg YO-01027 was injected intraperitoneally once daily for 14 days. Mouse tissues were collected, and formalin-fixed livers were impregnated in 30% sucrose solution and frozen with Tissue-Tek OCT complex. Ten microns thick frozen sections were stained with hematoxylin (H&E). The frozen sections were rinsed with tap water for 5min, with 60% isopropanol for 1min, and then stained with freshly prepared oil Red O solution for 15min. The sections were then rinsed with 60% isopropanol, followed by light staining of the nuclei with H&E for 15 seconds, and the sections were viewed under the microscope. |
Dosage form | 5µmol/kg/day for 14 days; i.p. |
Applications | YO-01027 treatment ameliorated liver steatosis in CoreTg mice and reduced expression of SREBP-1c without affecting body weight. |
References: | |
| Cas No. | 209984-56-5 | SDF | |
| 别名 | 二苯并氮卓,gamma-Secretase Inhibitor XX,YO01027 | ||
| 化学名 | (2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]-N-[(7S)-5-methyl-6-oxo-7H-benzo[d][1]benzazepin-7-yl]propanamide | ||
| Canonical SMILES | CC(C(=O)NC1C2=CC=CC=C2C3=CC=CC=C3N(C1=O)C)NC(=O)CC4=CC(=CC(=C4)F)F | ||
| 分子式 | C26H23F2N3O3 | 分子量 | 463.48 |
| 溶解度 | ≥ 23.174 mg/mL in DMSO, ≥ 4.13 mg/mL in EtOH with ultrasonic and warming | 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 | 2.1576 mL | 10.788 mL | 21.5759 mL |
| 5 mM | 431.5 μL | 2.1576 mL | 4.3152 mL |
| 10 mM | 215.8 μL | 1.0788 mL | 2.1576 mL |
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| 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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，
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2.
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Quality Control & SDS
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- Purity: >98.00%
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