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| Targets |
Sincalide ammonium acts as an agonist at cholecystokinin receptors (CCK1R and CCK2R). It binds selectively to CCK1 receptors (also known as CCK-A receptors) on gallbladder smooth muscle and pancreatic acinar cells to induce contraction and enzyme secretion . In cardiomyocytes, its protective effects are mediated through activation of the CCK1 receptor and the PI3K/Akt signaling pathway .
Sincalide targets the cholecystokinin 1 receptor (CCK1R) and cholecystokinin 2 receptor (CCK2R). [3][4] In H9c2 cardiomyoblast cells (rat embryonic heart-derived cell line), both CCK1R and CCK2R are expressed at mRNA and protein levels. The protective effect of CCK-8 against angiotensin II-induced apoptosis is primarily mediated through CCK1R, as the CCK1R antagonist Devazepide (10 μM) significantly blocked this effect, while the CCK2R antagonist L365260 (20 μM) did not. [3] |
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| ln Vitro |
As a new cardiovascular hormone, sincalide ammonium (Cholecystokinin octapeptide ammonium, or CCK-8 ammonium) significantly inhibits myocardial fibrosis in noninfarcted areas. Moreover, sincalide ammonium is beneficial in the battle against apoptosis, inflammation, and collagen deposition. H9c2 cardiomyoblasts are shielded from Ang II-induced apoptosis by CCK-8 (ammonium), in part because of the activation of the CCK1 receptor and the PI3K/Akt signaling pathway.
In H9c2 rat cardiomyoblast cells, sincalide ammonium (1 µM) protects against angiotensin II-induced apoptosis via activation of the CCK1 receptor and the PI3K/Akt signaling pathway. It significantly reduces the percentage of apoptotic cells (from 10.89% to 5.07% by flow cytometry) and reverses Ang II-induced changes in apoptotic markers by increasing p-Akt and Bcl-2 expression while decreasing Bax and cleaved-caspase-3 levels 。As a novel cardiovascular hormone, sincalide ammonium also exhibits a significant inhibitory effect on myocardial fibrosis in noninfarcted areas and plays a positive role in fighting inflammation, apoptosis, and collagen deposition 。 |
| ln Vivo |
In a MI rat model, sincalide ammonium (also known as Cholecystokinin octapeptide ammonium, or CCK-8 ammonium) reduces fibrosis in the noninfarcted areas and postpones left ventricular remodeling and the development of heart failure[4].
In a rat model of myocardial infarction (MI), intraperitoneal administration of sincalide ammonium (50 µg/kg/day) for 4 weeks significantly reduces fibrosis in non-infarcted areas, improves left ventricular ejection fraction (LVEF) (79.4% vs 43.3% in saline group), and delays left ventricular remodeling and the progression of heart failure 。 |
| Cell Assay |
Cell Viability Assay: Cells are seeded in 96-well plates and treated with compounds for 24 hours. Cell viability is assessed using the CCK-8 assay by measuring absorbance at 450 nm.
Apoptosis Detection: Apoptosis is detected using Annexin V-FITC/PI double staining and flow cytometry. Cells with Annexin V positivity are counted. Hoechst 33342 staining is also used to visualize nuclear condensation and fragmentation under fluorescence microscopy.
Western Blotting: Cells are lysed, and proteins are separated by SDS-PAGE, transferred to PVDF membranes, and probed with specific primary antibodies against CCKR, p-Akt, Akt, p-Bad, Bad, Bax, Bcl-2, and cleaved-caspase-3.
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| Animal Protocol |
Animal/Disease Models: MI rat model[4]
Doses: 50 μg/kg Route of Administration: ip; 50 μg/kg/d; for 4 weeks Experimental Results: Had significant inhibitory effect on myocardial fibrosis in noninfarcted areas. Model: Male Sprague-Dawley rats undergo left anterior descending coronary artery ligation to induce myocardial infarction (MI). Dosing: Sincalide ammonium is dissolved in sterile normal saline. The treatment group receives an intraperitoneal (i.p.) injection of 50 µg/kg/day (daily) for a total of 4 weeks. The control group receives an equal volume of normal saline. Assessment: After 4 weeks, echocardiography is performed to assess left ventricular function (LVEF, LVFS). Heart tissues are collected for histopathological examination (Masson's trichrome staining, immunohistochemistry) and protein expression analysis (Western blotting). |
| ADME/Pharmacokinetics |
Sincalide (the active moiety of the ammonium salt) is rapidly cleared from the circulation. Its serum half-life is less than 2 minutes 。Due to its peptide structure, oral absorption is negligible, and it is administered intravenously. It is likely degraded via proteolysis and is poorly absorbed orally.
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| Toxicity/Toxicokinetics |
Human Adverse Events: The most frequent adverse reactions associated with sincalide are gastrointestinal, including abdominal discomfort or pain and nausea, occurring in 20% or more of patients . Less common reactions include hypersensitivity (anaphylaxis, hypotension, bradycardia, rash), neurological (headache, seizures), and vasovagal reactions (dizziness, syncope) .
Reproductive Toxicity: Sincalide may cause preterm labor or spontaneous abortion and should be avoided near term. High doses in animals (122 times the human dose) caused developmental delays in offspring .
Contraindications: Known hypersensitivity, intestinal obstruction, and nursing mothers (due to unknown excretion in milk) .
General Safety: According to the Material Safety Data Sheet, sincalide ammonium is classified as "not a hazardous substance or mixture" under GHS standards for research use .
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| References |
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| Additional Infomation |
Proper infusion methodology: Sincalide cholescintigraphy for chronic acalculous gallbladder disease requires a 60-minute infusion of 0.02 μg/kg. Infusions of 3-15 minutes produce wide variability in gallbladder ejection fraction (GBEF) and cannot establish normal reference values; they also cause nausea and abdominal cramping in healthy subjects. With the 60-minute infusion, normal GBEF is ≥38%. Short infusions (3-15 minutes) may result in false-positive studies, potentially leading to unnecessary cholecystectomy. [2]
Alternative to sincalide: When sincalide is unavailable, pharmacy-compounded sincalide or fatty meals may be used. Fatty meals require >10 g fat and have established reference values (e.g., Ensure Plus: abnormal GBEF <33%; 250 mL milk: abnormal GBEF <51%). Fatty meals are problematic in patients with delayed gastric emptying (gastroparesis). [2] Sincalide for gallbladder emptying before cholescintigraphy: Indicated when patient has not eaten for >24 hours or is receiving hyperalimentation, to empty the gallbladder of viscous bile that may prevent entry of the hepatobiliary radiopharmaceutical. [2] Mechanism: Sincalide stimulates gallbladder contraction (approx. 50% volume evacuated within 15 minutes), relaxes the sphincter of Oddi, and stimulates pancreatic secretion of bicarbonate and protein. [1] |
| Molecular Formula |
C49H65N11O16S3
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|---|---|
| Molecular Weight |
1160.29950785637
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| Exact Mass |
1159.377
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| CAS # |
70706-98-8
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| Related CAS # |
Sincalide;25126-32-3
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| PubChem CID |
145712427
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| Sequence |
L-alpha-aspartyl-O4-sulfo-L-tyrosyl-L-methionyl-glycyl-L-tryptophyl-L-methionyl-L-alpha-aspartyl-L-phenylalaninamide ammonia
H-Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2.NH3 |
| SequenceShortening |
DXMGWMDF
D-{SO3H-Tyr}-MGWMDF-NH2 |
| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
14
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| Hydrogen Bond Acceptor Count |
20
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| Rotatable Bond Count |
33
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| Heavy Atom Count |
79
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| Complexity |
2180
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| Defined Atom Stereocenter Count |
7
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| SMILES |
S(C)CC[C@@H](C(N[C@H](C(N[C@H](C(N)=O)CC1C=CC=CC=1)=O)CC(=O)O)=O)NC([C@H](CC1=CNC2C=CC=CC1=2)NC(CNC([C@H](CCSC)NC([C@H](CC1C=CC(=CC=1)OS(=O)(=O)O)NC([C@H](CC(=O)O)N)=O)=O)=O)=O)=O.N
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| InChi Key |
SKHSHPLUIPFDPM-ITZXPNBCSA-N
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| InChi Code |
InChI=1S/C49H62N10O16S3.H3N/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);1H3/t32-,34-,35-,36-,37-,38-,39-;/m0./s1
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| 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;azane
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| Synonyms |
Sincalide (ammonium); Cholecystokinin octapeptide ammonium; CCK-8 ammonium; SQ19844 ammonium; Sincalide ammonium; 70706-98-8; CCK-8 (ammonium); orb1984051
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
H2O : 12.5 mg/mL (10.77 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8618 mL | 4.3092 mL | 8.6185 mL | |
| 5 mM | 0.1724 mL | 0.8618 mL | 1.7237 mL | |
| 10 mM | 0.0862 mL | 0.4309 mL | 0.8618 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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