Sograzepide (Netazepide) (Synonyms: Netazepide; YF 476; YM-220) |
| رقم الكتالوجGC31407 |
Sograzepide (Netazepide) (Netazepide ؛ YF 476 ؛ YM-220) هو أحد مضادات Gastrin / CCK-B شديدة الفعالية والانتقائية والنشطة عن طريق الفم مع قيمة IC50 تبلغ 0.1 نانومتر ، وله تأثير مثبط على نشاط Gastrin / CCK-A مع IC50 من 502 نانومتر.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 155488-25-8
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Sograzepide (Netazepide) is an oral active, selective and potent gastrin/CCK-B antagonist with an IC50 value of 0.1nM. It has inhibitory effects on the activity of gastrin/CCK-A and an IC50 value of 502nM. Sograzepide can specifically bind to the gastrin/CCK-B receptors in the rat brain, cloned canine, and cloned human tissues, with Ki values of 0.068, 0.62, and 0.19nM, respectively[1]. CCK-B is widely expressed throughout the human brain and gastrointestinal tract, and its expression is increased in various tumor cell lines (including gastric, lung, colon and lymphoma cells). Sograzepide can inhibit the expression of Pappalysin 2 in type 1 gastric neuroendocrine tumors and induce their regression, and can be used to treat gastric neuroendocrine tumors and pancreatic cancer caused by chronic autoimmune atrophic gastritis with hypergastrinemia[2].
In vitro, in AGS-E cells, pretreatment with Sograzepide (10-2, 10-1, 1, 10, 100nM) for 48 hours significantly eliminated the gastrin-dependent TFF2 promoter activity in a dose-dependent manner. At concentrations of 10-100nM gastrin, the responses of all TFF2 promoter constructs to gastrin were completely inhibited in the presence of 100nM Sograzepide. And 10-2nM Sograzepide inhibited 50% of the trans-activation effect of 100nM gastrin on the TFF2 promoter in AGS-E cells[3]. After treating AGSGR cells with Sograzepide (100nM) for 48h, the cell responses induced by gastrin, such as DNA synthesis, phosphatidylinositol hydrolysis, and histamine secretion, were all inhibited. Sograzepide has been shown to competitively replace gastrin-I with CCK-B with a higher efficacy than the previously developed CCK-B antagonists[4].
In vivo, by orally administering Sograzepide (2mg/kg/d, 5mg/kg/d) to Swiss mice for 8 days, it completely prevented the pain symptoms and nerve damage caused by vincristine, and had a protective effect on vincristine-induced peripheral neuropathy[2]. Sograzepide (300μM/kg) was subcutaneously injected once a week into Sprague-Dawley rats, which could prevent the increase in gastrin levels caused by proton pump inhibitors (PPI)-induced excessive gastric acid from causing the increase in ECL cell activity and density, gastric mucosa thickness, mucosal histamine decarboxylase (HDC) activity and serum gastrin levels[5].
References:
[1] Boyce M, Dowen S, Turnbull G, van den Berg F, Zhao CM, Chen D, Black J. Effect of Sograzepide, 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.
[2] Bernard A, Mroué M, Bourthoumieu S, Boyce M, Richard L, Sturtz F, Demiot C, Danigo A. Sograzepide, an Antagonist of Cholecystokinin Type 2 Receptor, Prevents Vincristine-Induced Sensory Neuropathy in Mice. Pharmaceuticals. 2024; 17(2):144.
[3] Tu S, Chi A L, Lim S H, et al. Gastrin regulates the TFF2 promoter through gastrin-responsive cis-acting elements and multiple signaling pathways[J]. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2007, 292(6): G1726-G1737.
[4] Lloyd K A. Investigation of biomarkers associated with hypergastrinaemia and their responses to CCK-2 receptor antagonism[M]. The University of Liverpool (United Kingdom), 2016.
[5] Chen D, Zhao C-M, Norlén P, Björkqvist M, Ding X-Q, Kitano M, Håkanson R: Effect of cholecystokinin-2 receptor blockade on rat stomach ECL cells. Cell Tissue Res 2000, 299:81-95. /Boyce M, Lloyd K A, Pritchard D M. Potential clinical indications for a CCK2 receptor antagonist[J]. Current Opinion in Pharmacology, 2016, 31: 68-75.
| Cell experiment [1]: | |
Cell lines | AGS-E cells |
Preparation Method | AGS-E cells (1.0 × 105 cells/well) were seeded in 12-well plates 24h before transfection. Cells were transfected with either 1.5μg TFF2-luciferase construct plasmid or 1.5μg empty reporter vector DNA using 4μl Superfectin. To confirm that gastrin activation of TFF2 transcription is dependent on the CCK-B, AGS-E cells were pretreated with CCK-B antagonist, Sograzepide, before gastrin stimulation. AGS-E cells were cotransfected with the TFF2-2584 plasmid or empty pGL2 vector and Renilla luciferase vector for 3h before gastrin treatment at the indicated dose in the absence or continuous presence of Sograzepide. The luciferase activities were determined by the dual-luciferase assay system 48h after transfection. |
Reaction Conditions | 10-2, 10-1, 1, 10, 100 nM; 48 hours |
Applications | The CCK-B antagonist Sograzepide pretreatment significantly abolished gastrin-dependent TFF2 promoter activity in a dose-dependent manner. The response of all TFF2 promoter constructs to 10-100nM of gastrin was completely inhibited in the presence of Sograzepide at 100nM. |
| Animal experiment [2]: | |
Animal models | Swiss mice |
Preparation Method | 1. Peripheral neuropathy was induced in mice by intraperitoneal injection of 100µg/kg of vincristine for 8 consecutive days. |
Dosage form | 2 or 5mg/kg/day for 8 days; p.o. |
Applications | Sograzepide completely prevented the painful symptoms and nerve injuries induced by vincristine. Sograzepide also showed protective effects against vincristine-induced peripheral neuropathy in a mouse model. |
References: | |
| Cas No. | 155488-25-8 | SDF | |
| المرادفات | 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 | ||
| Formula | C28H30N6O3 | M.Wt | 498.58 |
| الذوبان | DMSO : ≥ 100 mg/mL (200.57 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0057 mL | 10.0285 mL | 20.057 mL |
| 5 mM | 401.1 μL | 2.0057 mL | 4.0114 mL |
| 10 mM | 200.6 μL | 1.0028 mL | 2.0057 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 39 reference(s) in Google Scholar.)
GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *