Sograzepide (Netazepide)
(Synonyms: Netazepide; YF 476; YM-220) 目录号 : GC31407
Sograzepide (Netazepide)(Netazepide; YF 476; YM-220) 是一种极有效、高选择性和口服活性的 Gastrin/CCK-B 拮抗剂，IC50 值为 0.1 nM，对 Gastrin/CCK-A 活性有抑制作用，IC50 为 502纳米。
Cas No.:155488-25-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Sograzepide (Netazepide;YF476) is a gastrin/cholecystokinin 2 receptor (CCK2) antagonist.
[1]. Boyce M, et al. Effect of netazepide, a gastrin/CCK2 receptor antagonist, on gastric acid secretion and rabeprazole-induced hypergastrinaemia in healthy subjects. Br J Clin Pharmacol. 2015 May;79(5):744-55.
| Cas No. | 155488-25-8 | SDF | |
| 别名 | Netazepide; YF 476; YM-220 | ||
| Canonical SMILES | O=C(NC1=CC=CC(NC)=C1)N[C@H]2C(N(CC(C(C)(C)C)=O)C3=CC=CC=C3C(C4=NC=CC=C4)=N2)=O | ||
| 分子式 | C28H30N6O3 | 分子量 | 498.58 |
| 溶解度 | DMSO : ≥ 100 mg/mL (200.57 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 | 2.0057 mL | 10.0285 mL | 20.057 mL |
| 5 mM | 0.4011 mL | 2.0057 mL | 4.0114 mL |
| 10 mM | 0.2006 mL | 1.0028 mL | 2.0057 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。
Gastric Neuroendocrine Tumors (Carcinoids)
Purpose of review: The diagnosis of gastric neuroendocrine tumors (NETs) is being made with increased frequency likely as a result of more upper endoscopies being done for unrelated reasons. It is therefore vital that gastroenterologists become familiar with the basic work-up and management of patients found to have these tumors. This review describes the classification, pathophysiology, clinical characteristics, and treatment options of the different gastric NETs. Recent findings: In addition to the three traditional subtypes of gastric NETs, additional cases associated with achlorhydria and appropriate hypergastrinemia may exist. The management of gastric NETs between 1 and 2 cm in size remains controversial and needs to be individualized. Gastric NETs are uncommon but are now diagnosed more frequently. This review highlights the role of hypergastrinemia in their development and the controversies around their management.
Gastric neuroendocrine neoplasms: A review
Gastric neuroendocrine neoplasms (g-NENs) or neuroendocrine tumors are generally slow-growing tumors with increasing incidence. They arise from enterochromaffin like cells and are divided into four types according to clinical characteristic features. Type 1 and 2 are gastrin dependent, whereas type 3 and 4 are sporadic. The reason for hypergastrinemia is atrophic gastritis in type 1, and gastrin releasing tumor (gastrinoma) in type 2 g-NEN. The diagnosis of g-NENs needs histopathological investigation taken by upper gastrointestinal endoscopy. g-NENs are positively stained with chomogranin A and synaptophysin. Grading is made with mitotic index and ki-67 proliferation index on histopathological analysis. It is crucial to discriminate between types of g-NENs, because the management, treatment and prognosis differ significantly between subtypes. Treatment options for g-NENs include endoscopic resection, surgical resection with or without antrectomy, medical treatment with somatostatin analogues, netazepide or chemotherapy regimens. Follow-up without excision is another option in appropriate cases. The prognosis of type 1 and 2 g-NENs are good, whereas the prognosis of type 3 and 4 g-NENs are close to the prognosis of gastric adenocancer.
New Developments in Gastric Neuroendocrine Neoplasms
Purpose of review: Gastric neuroendocrine neoplasms (g-NENs) are a rare type of stomach cancer. The three main subtypes have different pathogeneses, biological behaviours and clinical characteristics, so they require different management strategies. This article will provide an overview of g-NENs and highlight recent advances in the field.
Recent findings: Molecular profiling has revealed differences between indolent and aggressive g-NENs, as well as a new somatic mutation responsible for some familial type I g-NENs. Novel biomarkers have been developed which will hopefully improve diagnosis, treatment, risk stratification and follow-up. Patient treatment is also changing, as evidence supports the use of less aggressive options (e.g. endoscopic surveillance or resection) in some patients with more indolent tumours. g-NEN heterogeneity poses challenges in understanding and managing this rare disease. More basic science research is needed to investigate molecular pathogenesis, and future larger clinical studies will hopefully also further improve treatment and patient outcomes.
[Chronic autoimmune gastritis : a multidisciplinary management]
Chronic autoimmune gastritis (CAG) is a continuum of histological changes in gastric mucosa including: atrophy, intestinal metaplasia, dysplasia and finally, the occurrence of a neoplasm (gastric Neuroendocrine Tumors -NETs- and adenocarcinoma). The association with Hashimoto and Graves-Basedow disease is known as the thyrogastric autoimmune syndrome. While Helicobacter pylori (Hp) infection may be associated with CAG, the role of the gastric microbiota is ill-defined. The gastric hypochlorhydria determines a malabsorption of different micronutrients (iron, magnesium, calcium, vitamin B12) as well as drugs (thyroxine, etc.). Pernicious anemia is favoured by the deficit of parietal intrinsic factor that contributes to B12 malabsorption. Serology for Hp, serum pepsinogen I/II, increased gastrin levels, the presence of parietal cell antibodies and intrinsic factor antibodies may reveal CAG. High definition endoscopy associated with virtual chromoendoscopy seems promising for CAG diagnosis and follow-up. NETs type 1 treatment includes: endoscopic and surgical resection, somatostatin analogues and the recent availability of netazepide, a gastrin antagonist. We review herein advances in the treatment and diagnosis of CAG and associated autoimmune disorders, which may involve, in a multidisciplinary way, all practitioners.
Netazepide Inhibits Expression of Pappalysin 2 in Type 1 Gastric Neuroendocrine Tumors
Background & aims: In patients with autoimmune atrophic gastritis and achlorhydria, hypergastrinemia is associated with the development of type 1 gastric neuroendocrine tumors (gNETs). Twelve months of treatment with netazepide (YF476), an antagonist of the cholecystokinin B receptor (CCKBR or CCK2R), eradicated some type 1 gNETs in patients. We investigated the mechanisms by which netazepide induced gNET regression using gene expression profiling.
Methods: We obtained serum samples and gastric corpus biopsy specimens from 8 patients with hypergastrinemia and type 1 gNETs enrolled in a phase 2 trial of netazepide. Control samples were obtained from 10 patients without gastric cancer. We used amplified and biotinylated sense-strand DNA targets from total RNA and Affymetrix (Thermofisher Scientific, UK) Human Gene 2.0 ST microarrays to identify differentially expressed genes in stomach tissues from patients with type 1 gNETs before, during, and after netazepide treatment. Findings were validated in a human AGSGR gastric adenocarcinoma cell line that stably expresses human CCK2R, primary mouse gastroids, transgenic hypergastrinemic INS-GAS mice, and patient samples.
Results: Levels of pappalysin 2 (PAPPA2) messenger RNA were reduced significantly in gNET tissues from patients receiving netazepide therapy compared with tissues collected before therapy. PAPPA2 is a metalloproteinase that increases the bioavailability of insulin-like growth factor (IGF) by cleaving IGF binding proteins (IGFBPs). PAPPA2 expression was increased in the gastric corpus of patients with type 1 gNETs, and immunohistochemistry showed localization in the same vicinity as CCK2R-expressing enterochromaffin-like cells. Up-regulation of PAPPA2 also was found in the stomachs of INS-GAS mice. Gastrin increased PAPPA2 expression with time and in a dose-dependent manner in gastric AGSGR cells and mouse gastroids by activating CCK2R. Knockdown of PAPPA2 in AGSGR cells with small interfering RNAs significantly decreased their migratory response and tissue remodeling in response to gastrin. Gastrin altered the expression and cleavage of IGFBP3 and IGFBP5.
Conclusions: In an analysis of human gNETS and mice, we found that gastrin up-regulates the expression of gastric PAPPA2. Increased PAPPA2 alters IGF bioavailability, cell migration, and tissue remodeling, which are involved in type 1 gNET development. These effects are inhibited by netazepide.