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].

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 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

MI rat model
50 μg/kg
i.p.; 50 μg/kg/d; for 4 weeks

Absorption, Distribution and Excretion
Intravenous injection (bolus) of syncallilide rapidly induces gallbladder contraction, reaching maximum contraction within 5 to 15 minutes, while gallbladder contraction induced by a fatty meal is progressive, reaching maximum contraction after approximately 40 minutes. Limited information is available regarding the elimination pathway of syncallilide. Limited information is available regarding the volume of distribution of syncallilide. Metabolism/Metabolites Limited information is available regarding the metabolism of syncallilide. Biological Half-Life Limited information is available regarding the half-life of syncallilide.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Sincalitone is a synthetic cholecystokinin octapeptide analog. Due to its molecular weight of 1143, sincalitone is likely to be present in very low concentrations in breast milk, and it is unlikely to be orally absorbed by the infant, as it is likely to be destroyed in the infant's gastrointestinal tract. Sincalitone has a serum half-life of less than 2 minutes, meaning that pausing breastfeeding for 10 minutes after administration ensures that the infant is not exposed to the drug.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

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Protein Binding
Limited information regarding protein binding of sincalitone.

[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.

Sincalide is an oligopeptide. Sincalide is an injectable drug used to aid in the diagnosis of gallbladder and pancreatic diseases. It has been identified as the 8-amino acid C-terminal fragment of cholecystokinin, also known as CCK-8. Naturally occurring cholecystokinin is a gastrointestinal peptide hormone that is generally essential for stimulating the digestion of proteins and fats in the body. Intravenous injection of sincalide can significantly reduce gallbladder volume by inducing gallbladder contraction. The resulting bile excretion is similar to the physiological bile excretion induced by endogenous cholecystokinin. In addition, sincalide can stimulate the pancreas to secrete bicarbonate and enzymes. Sincalide, marketed under the brand name Kinevac (FDA approved), is used to stimulate the duodenum, pancreas, and small intestine for cholesterol analysis, enzyme activity analysis, and X-ray examination, respectively. Sincalide is a cholecystokinin analogue. Sincalide is a synthetic C-terminal octapeptide with the same sequence as the endogenous cholecystokinin hormone. Sincalitone mimics the action of cholecystokinin, directly inducing gallbladder smooth muscle contraction, thereby reducing gallbladder volume and promoting bile emptying and pancreatic enzyme secretion. In addition, the drug also reduces lower esophageal sphincter tone and delays gastric emptying through the cholinergic signaling pathway. Cholecystokinin is an octapeptide hormone found in the intestines and brain. When secreted from the gastric mucosa, it stimulates the gallbladder to release bile and stimulates the pancreas to release digestive enzymes.

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Drug Indications
Sincalitone (trade name: Kinevac, FDA approved) is used for the following indications: (1) Stimulating gallbladder contraction, which can be assessed by various diagnostic imaging methods or by obtaining concentrated bile samples through duodenal aspiration for analysis of cholesterol, bile acids, phospholipids and crystals; (2) In combination with secretin, stimulating pancreatic secretion, followed by duodenal aspiration for analysis of enzyme activity, composition and cytology; (3) Accelerating the passage of barium meals through the small intestine, thereby reducing the time and radiation dose required for intestinal fluoroscopy and X-ray examination.
FDA Label

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Mechanism of Action
Intravenous administration of simcalitone causes gallbladder contraction, resulting in a significant reduction in gallbladder volume. The resulting bile expulsion is similar to physiological bile expulsion induced by endogenous cholecystokinin. Like cholecystokinin, simcalitone stimulates pancreatic secretion; co-administration with secretin increases the amount of pancreatic secretion and the output of bicarbonate and proteins (enzymes). The combined action of secretin and simcalitone allows for the assessment of specific pancreatic functions by measuring and analyzing duodenal aspirates.

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Pharmacodynamics
Following intravenous (bolus) administration of 0.02 mcg/kg simcalitone, the gallbladder reaches maximum contraction within 5 to 15 minutes. Simcalitone reduces the radiographic volume of the gallbladder by at least 40%, which is generally considered a satisfactory contraction.

C49H62N10O16S3

1143.26898

1142.35

C, 51.48; H, 5.47; N, 12.25; O, 22.39; S, 8.41

25126-32-3

Sincalide ammonium; 70706-98-8

9833444

White to off-white solid powder

1.4±0.1 g/cm3

1.643

2.25

13

19

33

78

2180

7

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

IZTQOLKUZKXIRV-YRVFCXMDSA-N

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

(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

CCK-8S; CCK 8S; CCK8S; Kinevac; CCK-8; CCK 8; CCK8

2934.99.9001

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.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O: ~50 mg/mL (~43.7 mM)
DMF: ~50 mg/mL (~43.7 mM)

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.

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 (Please use freshly prepared in vivo formulations for optimal results.)