HBX 41108
(Synonyms: 7-氯-9-氧代-9H-茚并[1,2-B]吡嗪-2,3-二甲腈) 目录号 : GC12622
HBX 41108是USP7的强效抑制剂，其IC50值为424nM。HBX 41108在体外和细胞中均能影响USP7介导的p53蛋白去泛素化。
Cas No.:924296-39-9
Sample solution is provided at 25 µL, 10mM.
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HBX 41108 is a potent inhibitor of USP7 with IC50 value of 424nM [1]. HBX 41108 is shown to affect USP7-mediated p53 deubiquitinating in vitro and in cells [1].
In vitro, HBX 41108 inhibited HCT116 proliferation in a dose-dependent manner with an IC50 value of 1μM. HBX 41108 induced the apoptosis of HCT116 in a dose-dependent manner within the concentration range of 0-16μM. Treatment with 1-10μM HBX 41108 for 24 hours resulted in a dose-dependent increase in the levels of p53 and its target gene products in HCT116. 10-50μM HBX 41108 for 24 hours increased the multi-ubiquitination level of p53 in 293T cells overexpressing USP7 [1]. 5μM HBX 41108 reduced cell cycle arrest and cell senescence in HUVECs treated with AGEs [2]. 20μM HBX 41108 for 2 hours abolished the increase in PPARγ stability induced by HAUSP in COS7 cells [3]. 10μM and 25μM HBX 41108 increased the hTPH2 promoter activity in a dose-dependent manner in RN46A cells [4].
In vivo, HBX 41108 (100mg/kg) decreased blood glucose levels and improved wound healing rate in diabetic rats, via intraperitoneal injection over 14 days [2].
References:
[1]. Colland F, Formstecher E, Jacq X, et al. Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells. Mol Cancer Ther. 2009;8(8):2286-2295.
[2]. Li X, Wang T, Tao Y, Wang X, Li L, Liu J. Inhibition of USP7 suppresses advanced glycation end-induced cell cycle arrest and senescence of human umbilical vein endothelial cells through ubiquitination of p53. Acta Biochim Biophys Sin (Shanghai). 2022;54(3):311-320.
[3]. Lee KW, Cho JG, Kim CM, et al. Herpesvirus-associated ubiquitin-specific protease (HAUSP) modulates peroxisome proliferator-activated receptor γ (PPARγ) stability through its deubiquitinating activity. J Biol Chem. 2013;288(46):32886-32896.
[4]. Nawa Y, Kaneko H, Oda M, et al. Functional characterization of the neuron-restrictive silencer element in the human tryptophan hydroxylase 2 gene expression. J Neurochem. 2017;142(6):827-840.
HBX 41108是USP7的强效抑制剂，其IC50值为424nM[1]。HBX 41108在体外和细胞中均能影响USP7介导的p53蛋白去泛素化[1]。
在体外，HBX 41108以剂量依赖的方式抑制HCT116细胞的增殖，其IC50值为1μM。HBX 41108在0-16μM的浓度范围内以剂量依赖的方式诱导HCT116细胞凋亡。用1-10μM的HBX 41108处理24小时，会导致HCT116细胞中p53及其靶基因产物的水平呈剂量依赖性增加。10-50μM的HBX 41108处理24小时会使过表达USP7的293T细胞中p53蛋白多泛素化水平升高[1]。5μM的HBX 41108能减缓AGEs处理的HUVECs中细胞周期停滞和细胞衰老[2]。20μM的HBX 41108处理2小时可抑制COS7细胞中HAUSP诱导的PPARγ稳定性的增加[3]。10μM和25μM的HBX 41108以剂量依赖的方式增加了RN46A细胞中hTPH2启动子的活性[4]。
在体内，以100mg/kg的剂量将HBX 41108腹腔注射到有伤口的糖尿病大鼠中，14天后大鼠血糖水平降低，伤口愈合率提高[2]。
| Cell experiment [1]: | |
Cell lines | HCT116 |
Preparation Method | The exponentially growing HCT116 cells were co-incubated with HBX 41108 for 24h, and then detect its effect on intracellular p53 levels. |
Reaction Conditions | 1, 3 and 10μM; 24h |
Applications | Western blot analysis revealed that the levels of p53 and its target gene products, such as the cyclin-dependent kinase inhibitor p21cip1/waf, increased in a dose-dependent manner with changes in HBX 41108 concentration. |
| Animal experiment [2]: | |
Animal models | SD rats; male; 4-6 weeks; 180-200g |
Preparation Method | Rats were randomized into three groups: in the control group, rats received saline; in the diabetic group, rats were intraperitoneal administrated with 60mg/kg STZ citrate buffer to induce diabetes (STZ group); in diabetes+HBX 41108 group, rats received 60mg/kg STZ citrate buffer and 100mg/kg HBX 41108 (HBX 41108 group). Intraperitoneal injected once a day for 14 consecutive days. Make skin wounds in the middle of the rats’ back with scissors. Blood and wounds were detected on day 0, 7 and 14. Wound tissue was collected on days 0, 7, and 14 for HE staining. Western blot analysis the expression of USP7, p53, and p21 in wound tissue. |
Dosage form | 100mg/kg/d; 14d; i.p. |
Applications | STZ group had higher blood glucose levels than control group on day 0, 7 and 14 post injury. HBX 41108 group decreased blood glucose levels on 14 post injury. STZ significantly reduced the wound healing rate, whereas the application of HBX 41108 could rescue the STZ-mediated effects. HE showed that newly formed in wounds treated with HBX 41108 on day 7 post-injury. Meanwhile, on day 7 and day 14, the expressions of USP7, p53, and p21 were found to be increased by STZ and decreased by the application of HBX 41108. |
References: | |
| Cas No. | 924296-39-9 | SDF | |
| 别名 | 7-氯-9-氧代-9H-茚并[1,2-B]吡嗪-2,3-二甲腈 | ||
| 化学名 | 7-chloro-9-oxo-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile | ||
| Canonical SMILES | ClC1=CC=C(C2=NC(C#N)=C(C#N)N=C2C3=O)C3=C1 | ||
| 分子式 | C13H3ClN4O | 分子量 | 266.64 |
| 溶解度 | 33mg/mL in DMSO; 25mg/mL in DMF; | 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.7504 mL | 18.7519 mL | 37.5038 mL |
| 5 mM | 750.1 μL | 3.7504 mL | 7.5008 mL |
| 10 mM | 375 μL | 1.8752 mL | 3.7504 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 | ||||||||||
| 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.
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Quality Control & SDS
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- Purity: >98.00%
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