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Sincalide (CCK-8) is a cholecystokinetic drug used to treat cholecystitis and to diagnose disorders of the gallbladder and pancreas. It is cholecystokinin's 8-amino acid C-terminal fragment. The brain and intestines contain the octapeptide hormone sincalide. It is secreted from the mucosa of the stomach and causes the gallbladder to release bile and the pancreas to release digestive enzymes.
Physicochemical Properties
| Molecular Formula | C49H62N10O16S3 |
| Molecular Weight | 1143.26898 |
| Exact Mass | 1142.35 |
| Elemental Analysis | C, 51.48; H, 5.47; N, 12.25; O, 22.39; S, 8.41 |
| CAS # | 25126-32-3 |
| Related CAS # | Sincalide ammonium; 70706-98-8 |
| PubChem CID | 9833444 |
| Appearance | White to off-white solid powder |
| Density | 1.4±0.1 g/cm3 |
| Index of Refraction | 1.643 |
| LogP | 2.25 |
| Hydrogen Bond Donor Count | 13 |
| Hydrogen Bond Acceptor Count | 19 |
| Rotatable Bond Count | 33 |
| Heavy Atom Count | 78 |
| Complexity | 2180 |
| Defined Atom Stereocenter Count | 7 |
| SMILES | CSCC[C@H](NC([C@@H](NC([C@@H](N)CC(O)=O)=O)CC1=CC=C(OS(=O)(O)=O)C=C1)=O)C(NCC(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N)=O)CC2=CC=CC=C2)=O)CC(O)=O)=O)CCSC)=O)CC3=CNC4=CC=CC=C34)=O)=O |
| InChi Key | IZTQOLKUZKXIRV-YRVFCXMDSA-N |
| InChi Code | InChI=1S/C49H62N10O16S3/c1-76-18-16-34(55-47(69)37(58-44(66)32(50)23-41(61)62)21-28-12-14-30(15-13-28)75-78(72,73)74)45(67)53-26-40(60)54-38(22-29-25-52-33-11-7-6-10-31(29)33)48(70)56-35(17-19-77-2)46(68)59-39(24-42(63)64)49(71)57-36(43(51)65)20-27-8-4-3-5-9-27/h3-15,25,32,34-39,52H,16-24,26,50H2,1-2H3,(H2,51,65)(H,53,67)(H,54,60)(H,55,69)(H,56,70)(H,57,71)(H,58,66)(H,59,68)(H,61,62)(H,63,64)(H,72,73,74)/t32-,34-,35-,36-,37-,38-,39-/m0/s1 |
| Chemical Name | (3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1-oxo-3-(4-sulfooxyphenyl)propan-2-yl]amino]-4-oxobutanoic acid |
| Synonyms | CCK-8S; CCK 8S; CCK8S; Kinevac; CCK-8; CCK 8; CCK8 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | Sincalide (Cholecystokinin octapeptide, CCK‐8), a novel cardiovascular hormone, significantly inhibits myocardial fibrosis in noninfarcted regions. Additionally, CCK-8 is beneficial in the fight against apoptosis, inflammation, and collagen deposition. In part, CCK-8 prevents Ang II-induced apoptosis in H9c2 cardiomyoblasts by activating the CCK1 receptor and PI3K/Akt (phosphatidylinositol-3 kinase/protein kinase B) signaling pathway[3]. |
| ln Vivo | Sincalide (Cholecystokinin octapeptide, CCK‐8) (i.p.; 50 μg/kg/d; for 4 weeks) reduces fibrosis in the noninfarcted areas and delays the development of heart failure and left ventricular remodeling in a MI rat model[4]. |
| Cell Assay |
Cell Line: H9c2 cells Concentration: 0.001, 0.01, 0.1, 1, 10, or 100 μmol/L Incubation Time: 24 h Result: Attenuated Ang II‐induced toxicity in H9c2 cells |
| Animal Protocol |
MI rat model 50 μg/kg i.p.; 50 μg/kg/d; for 4 weeks |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion The intravenous (bolus) administration of sincalide causes a prompt contraction of the gallbladder that becomes maximal in 5 to 15 minutes, as compared with the stimulus of a fatty meal which causes a progressive contraction that becomes maximal after approximately 40 minutes. Limited information is available on the route of elimination of sincalide Limited information is available on the volume of distribution of sincalide. Metabolism / Metabolites Limited information is available on the metabolism of sincalide. Biological Half-Life Limited information is available on the half-life of sincalide. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Sincalide is a synthetic octapeptide analogue of cholecystokinin. Because sincalide has a molecular weight of 1143, the amount in milk is likely to be very low and oral absorption by the infant is unlikely because it is probably destroyed in the infant's gastrointestinal tract. The serum half-life of sincalide is less than 2 minutes, indicating that withholding breastfeeding for 10 minutes after a dose should ensure that the infant is not exposed to the drug. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Limited information is available on the protein binding of sincalide. |
| References |
[1]. Kinevac (sincalide for injection)/Squibb Diagnostics. Gastroenterol Nurs. 1991 Oct;14(2):98-100. [2]. Sincalide: A Review of Clinical Utility, Proper Infusion Methodology, and Alternative Cholecystogogues. J Nucl Med Technol. 2019 Sep;47(3):210-212. [3]. Protective effect of cholecystokinin octapeptide on angiotensin II-induced apoptosis in H9c2 cardiomyoblast cells. J Cell Biochem. 2020 Jul;121(7):3560-3569. [4]. Cholecystokinin octapeptide reduces myocardial fibrosis and improves cardiac remodeling in post myocardial infarction rats. Int J Biochem Cell Biol. 2020 Aug;125:105793. |
| Additional Infomation |
Sincalide is an oligopeptide. Sincalide is a medication given by injection to assist in the diagnosis of gallbladder and pancreas disorders. It is identified as the 8-amino acid C-terminal segment of cholecystokinin and is also known as CCK-8. Naturally occurring cholecystokinin is a gastrointestinal peptide hormone normally essential for stimulating protein and fat digestion in the body. When injected intravenously, sincalide produces a substantial reduction in gallbladder size by causing this organ to contract. The evacuation of bile that results is similar to that which occurs physiologically in response to endogenous cholecystokinin. Furthermore, sincalide stimulates the pancreatic secretion of bicarbonate and enzymes. As the product Kinevac (FDA), sincalide is used to stimulate the duodenum, pancreas, and small bowel for cholesterol analysis, enzymatic activity analysis, and x-ray examination respectively. Sincalide is a Cholecystokinin Analog. Sincalide is a synthetic C-terminal octapeptide identical to the sequences of the endogenous cholecystokinin hormone. Mimic action of cholecystokinin, sincalide induces gallbladder smooth muscle contraction directly, thereby reducing gallbladder size, inducing bile evacuation, and secretion of pancreatic enzymes. In addition, this agent decreases esophageal sphincter tone and delays gastric emptying via cholinergic signaling. An octapeptide hormone present in the intestine and brain. When secreted from the gastric mucosa, it stimulates the release of bile from the gallbladder and digestive enzymes from the pancreas. Drug Indication As the product Kinevac (FDA), sincalide is used for the following indications: 1) to stimulate gallbladder contraction, as may be assessed by various methods of diagnostic imaging, or to obtain by duodenal aspiration a sample of concentrated bile for analysis of cholesterol, bile salts, phospholipids, and crystals; (2) to stimulate pancreatic secretion in combination with secretin prior to obtaining a duodenal aspirate for analysis of enzyme activity, composition, and cytology; (3) to accelerate the transit of a barium meal through the small bowel, thereby decreasing the time and extent of radiation associated with fluoroscopy and x-ray examination of the intestinal tract. FDA Label Mechanism of Action When injected intravenously, sincalide produces a substantial reduction in gallbladder size by causing this organ to contract. The evacuation of bile that results is similar to that which occurs physiologically in response to endogenous cholecystokinin. Like cholecystokinin, sincalide stimulates pancreatic secretion; concurrent administration with secretin increases both the volume of pancreatic secretion and the output of bicarbonate and protein (enzymes) by the gland. This combined effect of secretin and sincalide permits the assessment of specific pancreatic function through measurement and analysis of the duodenal aspirate. Pharmacodynamics Following an intravenous (bolus) injection of 0.02 mcg/kg of sincalide, maximal contraction of the gallbladder occurred in 5 to 15 minutes. Sincalide reduced gallbladder radiographic size by at least 40%, generally considered satisfactory contraction. |
Solubility Data
| Solubility (In Vitro) |
H2O: ~50 mg/mL (~43.7 mM) DMF: ~50 mg/mL (~43.7 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.19 mM) (saturation unknown) in 10% DMF 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |