Sincalide (CCK-8)
(Synonyms: 辛卡利特; Cholecystokinin octapeptide; CCK-8; SQ19844) 目录号 : GC32749
辛卡胺（Sincalide CCK-8）是CCK的一个次要生物活性片段
Cas No.:25126-32-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
H9c2 cells |
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Preparation Method |
H9c2 cells were incubated with sincalide (0.001, 0.01, 0.1, 1, 10, or 100µM) or Ang II (0.01, 0.1, 1, or 10µM) for 24 hours. Then treated the cells with sincalide at various concentrations (0.001, 0.01, 0.1, 1, 10, 100µM) before adding Ang II. |
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Reaction Conditions |
0.001, 0.01, 0.1, 1, 10, or 100µM |
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Applications |
Treatment with 1µM sincalide before exposure to 1µM Ang II significantly prevented cell death. |
| Animal experiment [2]: | |
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Animal models |
Male Sprague-Dawley rats (200-220g, 6-7 weeks) |
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Preparation Method |
Sincalide was dissolved in sterile normal saline to form a 50µg/mL stock solution. Male Sprague-Dawley rats were separated into 3 groups: sham operation, MI+NaCl, and MI+sincalide. All rats were subjected to left coronary artery ligation to induce MI or sham operation and then treated with sincalide or saline for 28 days. |
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Dosage form |
50µg/kg/d sincalide，intraperitoneal injection |
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Applications |
Treatment with sincalide attenuated myocardial infarction-induced myocardial fibrosis, and delay the left ventricular remodeling and the progress of heart failure. |
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References: [1]. Wang C, Yu H, et al. Protective effect of cholecystokinin octapeptide on angiotensin II-induced apoptosis in H9c2 cardiomyoblast cells. J Cell Biochem. 2020;121(7):3560-3569. [2]. Wang C, Zhang C, et al. Cholecystokinin octapeptide reduces myocardial fibrosis and improves cardiac remodeling in post myocardial infarction rats. Int J Biochem Cell Biol. 2020;125:105793. |
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Sincalide(CCK-8) is a minor bioactive segment of CCK that retains most of the biological activities of CCK and is widely used to study CCK functions[1]. Sincalide is a rapid-acting, synthetic analog of cholecystokinin for intravenous use in postevacuation cholecystography, and has a variety of effects as a novel cardiovascular hormone[2,3].
Sincalide protects H9c2 cardiomyoblasts from Ang II-induced apoptosis partly via activation of the CCK1 receptor and the phosphatidyqinositol-3 kinase/protein kinase B (PI3K/Akt) signaling pathway[1]. Sincalide can protect human retinal pigment epithelial cells against apoptosis induced by peroxynitrite[4]. Sincalide dose-dependently inhibited METH-induced cytotoxic effect by activating the CCK2 receptor subtype in PC12 cells and CCK2 receptor stable transfected-HEK293 cells[5]
Sincalide can alleviate fibrosis in the noninfarcted regions and delay the left ventricular remodeling and the progress of heart failure in a MI rat model[2]. Sincalide decreased RPE cells apoptosis partly induced by ONOO- in Sprague-Dawley rats and is a potential drug for therapy of diabetic retinopathy[6]. Intramuscular injection of sincalide (0.07μg/kg) induced remarkable contractions of the gallbladder in vivo, and the contraction was nearly abolished by premedication of atropine sulfate (0.015 mg/kg)[7]
References:
[1]. Wang C, Yu H, et al. Protective effect of cholecystokinin octapeptide on angiotensin II-induced apoptosis in H9c2 cardiomyoblast cells. J Cell Biochem. 2020;121(7):3560-3569.
[2]. Wang C, Zhang C, et al. Cholecystokinin octapeptide reduces myocardial fibrosis and improves cardiac remodeling in post myocardial infarction rats. Int J Biochem Cell Biol. 2020;125:105793.
[3]. Maher KA. Kinevac (sincalide for injection)/Squibb Diagnostics. Gastroenterol Nurs. 1991;14(2):98-100.
[4]. Liu Y, Zhang Y, et al. Cholecystokinin octapeptide antagonizes apoptosis in human retinal pigment epithelial cells. Neural Regen Res. 2014;9(14):1402-1408.
[5]. Wen D, An M, et al. Cholecystokinin-8 inhibits methamphetamine-induced neurotoxicity via an anti-oxidative stress pathway. Neurotoxicology. 2016;57:31-38.
[6]. Hao LN, Wang M, et al. Control of peroxyntrite-induced production of inducible nitric oxide synthase isoforms and antagonism of cholecystokinin octapeptide -8 in retinal pigment epithelial cells in vivo. Int J Ophthalmol. 2011;4(6):605-610.
[7]. Takahashi T, Yamamura T, et al. Effects of cholecystokinin-octapeptide on the human gallbladder both in vivo and in vitro. Gastroenterol Jpn. 1986;21(1):49-54.
辛卡利特(CCK-8)是CCK的一个次要生物活性片段，保留了CCK的大部分生物活性，被广泛用于研究CCK的功能[1]。辛卡利特是一种速效合成胆囊收缩素类似物，用于静脉内清空胆囊造影术，作为一种新型心血管激素具有多种作用[2,3]。
Sincalide 部分通过激活 CCK1 受体和磷脂酰肌醇-3 激酶/蛋白激酶 B (PI3K/Akt) 信号通路来保护 H9c2 心肌细胞免受 Ang II 诱导的细胞凋亡[1]。辛卡利特可以保护人视网膜色素上皮细胞免受过氧亚硝酸盐诱导的细胞凋亡[4]。辛卡利特通过激活 PC12 细胞和 CCK2 受体稳定转染的 HEK293 细胞中的 CCK2 受体亚型剂量依赖性地抑制 METH 诱导的细胞毒性作用[5]
辛卡利特可减轻心肌梗死大鼠模型的非梗死区纤维化，延缓左心室重构和心力衰竭进展[2]。 Sincalide 可降低 Sprague-Dawley 大鼠部分由 ONOO- 诱导的 RPE 细胞凋亡，是治疗糖尿病视网膜病变的潜在药物[6]。肌内注射辛卡利特（0.07μg/kg）可引起体内胆囊显着收缩，术前给予硫酸阿托品（0.015 mg/kg）后收缩几乎消失[7]
| Cas No. | 25126-32-3 | SDF | |
| 别名 | 辛卡利特; Cholecystokinin octapeptide; CCK-8; SQ19844 | ||
| Canonical SMILES | Asp-{SO3H-Tyr}-Met-Gly-Trp-Met-Asp-Phe-NH2 | ||
| 分子式 | C49H62N10O16S3 | 分子量 | 1143.27 |
| 溶解度 | DMSO : 16.67 mg/mL (14.58 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C,protect from light |
| 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 | 0.8747 mL | 4.3734 mL | 8.7468 mL |
| 5 mM | 0.1749 mL | 0.8747 mL | 1.7494 mL |
| 10 mM | 0.0875 mL | 0.4373 mL | 0.8747 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。
Inhibitory Effect of CCK-8 on Methamphetamine-Induced Apoptosis
Fa Yi Xue Za Zhi 2021 Dec 25;37(6):796-805.PMID:35243844DOI:10.12116/j.issn.1004-5619.2021.310206.
Objectives: To investigate the inhibitory effect of cholecystokinin octapeptide (CCK-8) binding to cholecystokinin 2 receptor (CCK2R) on methamphetamine (METH)-induced neuronal apoptosis, and to explore the signal transduction mechanism of β-arrestin 2 in CCK-8 inhibiting METH-induced neuronal apoptosis. Methods: SH-SY5Y cell line was cultured, and HEK293-CCK1R and HEK293-CCK2R cell line were constructed by lentivirus transfection. Small interfering RNA (siRNA) was used to knockdown the expression of β-arrestin 2. Annexin Ⅴ-FITC/PI staining and flow cytometry were used to detect the apoptotic rate of cells, and Western blotting was used to detect the expression of apoptosis-related proteins. Results: The apoptosis of SH-SY5Y cells was induced by 1 mmol/L and 2 mmol/L METH treatment, the number of nuclear fragmentation and pyknotic cells was significantly increased, and the expression of apoptosis-related proteins Bax and cleaved caspase-3 were increased. CCK-8 pre-treatment at the dose of 0.1 mmol/L and 1 mmol/L significantly reversed METH-induced apoptosis in SH-SY5Y cells, and inhibited cell nuclear fragmentation, pyknosis and the changes of apoptosis-related proteins induced by METH. In lentivirus transfected HEK293-CCK1R and HEK293-CCK2R cells, the results revealed that CCK-8 had no significant effect on METH-induced changes of apoptosis-related proteins in HEK293-CCK1R cells, but it could inhibit the expression level of apoptosis-related proteins in HEK293-CCK2R cells induced by METH. The inhibitory effect of CCK-8 on METH-induced apoptosis was blocked by the knockdown of β-arrestin 2 expression in SH-SY5Y cells. Conclusions: CCK-8 can bind to CCK2R and exert an inhibitory effect on METH-induced apoptosis by activating the β-arrestin 2 signal.
Sincalide: A Review of Clinical Utility, Proper Infusion Methodology, and Alternative Cholecystogogues
J Nucl Med Technol 2019 Sep;47(3):210-212.PMID:31019045DOI:10.2967/jnmt.119.226019.
Sincalide (Kinevac) is widely used in conjunction with cholescintigraphy for a variety of clinical indications. Over the years, numerous publications have verified the optimal infusion methodology. Published data and consensus recommendations emphasize that Sincalide, 0.02 μg/kg, should be infused over 60 min. Production problems sometimes limit the availability of Sincalide. In that case, non-Food and Drug Administration pharmacy-compounded Sincalide may serve as an alternative. Fatty meals have also been used. Various illnesses and drugs may inhibit gallbladder contraction. Thus, these drugs should be withheld for 48 h before the study. Sincalide cholescintigraphy is most commonly used to diagnose or exclude chronic acalculous gallbladder disease. The study should preferably be performed as an outpatient procedure.
A necroptosis related prognostic model of pancreatic cancer based on single cell sequencing analysis and transcriptome analysis
Front Immunol 2022 Oct 7;13:1022420.PMID:36275722DOI:10.3389/fimmu.2022.1022420.
Background: As a tumor type with high mortality and poor therapeutic effect, the pathogenesis of pancreatic cancer is still unclear. It is necessary to explore the significance of necroptosis in pancreatic cancer. Methods: Pancreatic cancer transcriptome data were obtained from the TCGA database, ICGC database, and GSE85916 in the GEO database. The TCGA cohort was set as a training cohort, while the ICGC and GSE85916 cohort were set as the validation cohorts. Single-cell sequencing data of pancreatic cancer were obtained from GSE154778 in the GEO database. The genes most associated with necroptosis were identified by weighted co-expression network analysis and single-cell sequencing analysis. COX regression and Lasso regression were performed for these genes, and the prognostic model was established. By calculating risk scores, pancreatic cancer patients could be divided into NCPTS_high and NCPTS_low groups, and survival analysis, immune infiltration analysis, and mutation analysis between groups were performed. Cell experiments including gene knockdown, CCK-8 assay, clone formation assay, transwell assay and wound healing assay were conducted to explore the role of the key gene EPS8 in pancreatic cancer. PCR assays on clinical samples were further used to verify EPS8 expression. Results: We constructed the necroptosis-related signature in pancreatic cancer using single-cell sequencing analysis and transcriptome analysis. The calculation formula of risk score was as follows: NCPTS = POLR3GL * (-0.404) + COL17A1 * (0.092) + DDIT4 * (0.007) + PDE4C * (0.057) + CLDN1 * 0.075 + HMGA2 * 0.056 + CENPF * 0.198 +EPS8 * 0.219. Through this signature, pancreatic cancer patients with different cohorts can be divided into NCPTS_high and NCPTS_low group, and the NCPTS_high group has a significantly poorer prognosis. Moreover, there were significant differences in immune infiltration level and mutation level between the two groups. Cell assays showed that in CAPAN-1 and PANC-1 cell lines, EPS8 knockdown significantly reduced the viability, clonogenesis, migration and invasion of pancreatic cancer cells. Clinical PCR assay of EPS8 expression showed that EPS8 expression was significantly up-regulated in pancreatic cancer (*P<0.05). Conclusion: Our study can provide a reference for the diagnosis, treatment and prognosis assessment of pancreatic cancer.
Sincalide in patients with parenteral nutrition-associated gallbladder disease
Ann Pharmacother 2004 Nov;38(11):1942-5.PMID:15316105DOI:10.1345/aph.1E153.
Objective: To review the role of Sincalide in treating and preventing parenteral nutrition (PN)-associated gallbladder disease. Data sources: A MEDLINE (1996-March 2004) search was performed using the key terms cholecystokinin, Sincalide, parenteral nutrition, cholelithiasis, cholestasis, and sludge. Data synthesis: Five human studies investigated the safety and efficacy of Sincalide in patients with PN-associated gallbladder disease. Sincalide at intravenous doses of 0.04 microg/kg 3 times daily increased bile flow and improved serum bilirubin levels. However, patients with advanced liver disease did not respond to Sincalide therapy. Long-term follow-up data on Sincalide effects on liver disease progression are not yet available. Conclusions: Sincalide improved the signs of cholestasis. However, its long-term effects in preventing and treating PN-associated gallbladder disease remain unknown and its routine use for this indication cannot be recommended at this time.
(pGlu-Gln)-CCK-8[mPEG]: a novel, long-acting, mini-PEGylated cholecystokinin (CCK) agonist that improves metabolic status in dietary-induced diabetes
Biochim Biophys Acta 2013 Aug;1830(8):4009-16.PMID:23583730DOI:10.1016/j.bbagen.2013.04.004.
Background: Cholecystokinin (CCK) is a gastrointestinal hormone that has been proposed as a potential therapeutic option for obesity-diabetes. As such, (pGlu-Gln)-CCK-8 is an N-terminally modified CCK-8 analogue with improved biological effectiveness over the native peptide. Methods: The current study has examined the in vitro stability, biological activity and in vivo therapeutic applicability of a novel second generation mini-PEGylated form of (pGlu-Gln)-CCK-8, (pGlu-Gln)-CCK-8[mPEG]. Results: (pGlu-Gln)-CCK-8[mPEG] was completely resistant to enzymatic degradation and in addition displayed similar insulinotropic (p<0.05 to p<0.001) and satiating effects (p<0.01 to p<0.001) as (pGlu-Gln)-CCK-8. This confirmed the capability of (pGlu-Gln)-CCK-8[mPEG] to bind to and activate the CCK receptor. Sub-chronic twice daily injection of (pGlu-Gln)-CCK-8[mPEG] in high fat fed mice for 35days significantly decreased body weight gain (p<0.05), food intake (p<0.01 to p<0.001) and triacylglycerol deposition in liver (p<0.001) and muscle (p<0.001). Furthermore, (pGlu-Gln)-CCK-8[mPEG] markedly improved intraperitoneal glucose tolerance (p<0.05) and insulin sensitivity (p<0.001). Despite this therapeutic profile, once daily injection of (pGlu-Gln)-CCK-8[mPEG] in high fat fed mice for 33days, at the same dose, was not associated with alterations in food intake and body weight. In addition, metabolic responses to exogenous glucose and insulin injection were similar to saline treated controls. Conclusion: These studies emphasise the therapeutic potential of (pGlu-Gln)-CCK-8[mPEG] and similar molecules. General significance: A more detailed analysis of the dose and administration schedule employed for (pGlu-Gln)-CCK-8[mPEG] could provide a novel and effective compound to treat obesity-diabetes.