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Purity: ≥98%
| Targets |
CCK receptor
Caerulein targets cholecystokinin (CCK) receptors. Its primary mechanism of action involves mimicking the endogenous effects of CCK, leading to the stimulation of pancreatic enzyme biosynthesis and secretion, as well as the contraction of specific smooth muscle tissues. Caerulein stimulates biosynthesis of pancreatic enzymes in AR4-2J pancreatic cells in vitro. It induces acute pancreatitis in mice. Caerulein also enhances proteasome activity in Gdeg mice. |
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| ln Vitro |
CeruLetide chemically and biologically interacts with the human gastrointestinal tract cholecystokinin-cholecystin (CCK) and gastrin II profiles. CeruLetide stimulates gallbladder contractions, extrapancreatic, gastric fluid and motility in the ICU duodenum, jejunum, ileum and sleep, while delaying gastric emptying and inhibiting motility in the proximal duodenum [1]. CeruLetide activates NF-kappaB/Rel in vitro at minimal physiological doses. This activation may induce a genetic program of self-defense before cellular damage occurs, which may terminate the higher degree of damage to pancreatic alveolar cells that occurs after chronic stress overstress [2].
In vitro, caerulein is a CCK agonist that stimulates biosynthesis of pancreatic enzymes in AR4-2J pancreatic cells. It is used to study cell signaling mediated by NF-kappaB upregulation of proteins such as intercellular adhesion molecule-1 (ICAM-1) and inflammation related molecules such as NADPH oxidase and Janus kinase signal transducer. Caerulein's effects on pancreatic acinar cells have been extensively studied in vitro. |
| ln Vivo |
Ceruletide can be used in animal modeling to construct animal pancreatitis models. CeruLetide (0.4-0.5 μg/kg, intravenous; 3-4 μg/kg, subcutaneous) causes vomiting and defecation in conscious intact dogs 15-30 minutes after intravenous injection and 2-4 hours after full recovery after sc administration. CeruLetide (5-15 ng/kg, iv) exhibits significant spasmogenic effects on the fecal pylorus. CeruLetide also reduces blood sugar in anesthetized dogs [1]. CeruLetide serum bile acid (SBA) stimulation circumvents the exogenous and endogenous effects associated with postprandial (PP) SBA stimulation. CeruLetide SBA stimulation may be as effective as PP SBA stimulation in dogs with cardiac portosystemic shunts (PSS) and may be more sensitive to liver dysfunction in dogs with confirmed respiratory disease (URD) [3].
In vivo, caerulein induces acute pancreatitis in mice. It stimulates gastric, biliary, and pancreatic secretion, as well as certain smooth muscles. Caerulein is used as a diagnostic aid in pancreatic malfunction and in paralytic ileus. The compound prevents gallbladder pain. Caerulein enhances proteasome activity in Gdeg mice. |
| Enzyme Assay |
Nuclear appearance of NF-kappaB/Rel-binding activity was detectable 15 minutes after cerulein injection. The DNA-binding activity consisted of NF-kappaB1 p50, NF-kappaB2 p52, and RelA p65 as judged by supershift assays and Western blot analysis. The onset and termination of NF-kappaB/Rel activation correlated with the degradation and reappearance of IkappaBalpha. Cerulein in supramaximal but not in physiological doses activated NF-kappaB/Rel in vitro. After blocking of NF-kappaB/Rel activation with pyrrolidine dithiocarbamate, the degree of morphological alterations was more pronounced than in controls, serum amylase and lactate dehydrogenase levels were significantly increased, and messenger RNA levels of pancreatitis-associated protein were more strongly induced, reflecting a more severe degree of pancreatitis. Similar results were obtained when N-acetyl-L-cysteine was used as an inhibitor of NF-kappaB activation.
Conclusions: These data show that NF-kappaB/Rel is rapidly activated during cerulein pancreatitis. This activation may induce a self-defending genetic program before the onset of cellular injury, which might prevent higher degrees of damage of pancreatic acinar cells after secretagogue hyperstimulation.[3]
In vitro receptor binding assays for caerulein involve measuring its binding affinity to cholecystokinin (CCK) receptors. The receptor is incubated with a radiolabeled ligand and varying concentrations of caerulein. The displacement of the radiolabeled ligand is measured, and the IC50 or Ki value is calculated. The compound's functional activity is assessed using calcium flux assays or cAMP accumulation assays in cells expressing CCK receptors. |
| Cell Assay |
In vitro cell-based assays for caerulein evaluate its effects on pancreatic acinar cells. AR4-2J pancreatic cells are cultured and treated with caerulein, and the biosynthesis of pancreatic enzymes is measured using ELISA or enzymatic assays. The compound's effects on cell signaling, including NF-kappaB activation and ICAM-1 expression, are assessed using Western blot or qPCR. Cell viability is assessed using MTT or LDH release assays.
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| Animal Protocol |
Dogs: Serum bile acid (SBA) stimulation is administered to all dogs using food (<5 kg/body weight [BW] 2 teaspoons, >5 kg BW 2 tablespoons) or Ceruletide IM (0.3 μg/kg BW) on consecutive days. To reduce metabolic complications such as hepatic encephalopathy, a diet high in fiber and moderate in protein is recommended. The dogs fast for twelve hours prior to each test. At baseline, 60 and 120 minutes after feeding, and 20, 30, and 40 minutes after injection, blood samples are taken, in that order. The serum is used to measure SBA by a colorimetric test with endpoint determination after the blood samples are collected in plain tubes and allowed to clot. The samples are then centrifuged at 6,500 ×g for one minute[3].
Animals with portosystemic shunt (PSS) (n = 11) and dogs with upper respiratory disease (URD) (n = 9) were investigated. Healthy dogs (n = 13) and dogs with other diseases (n = 17) served as controls. Methods: All dogs underwent SBA stimulation with food and ceruletide. Stimulation blood samples were drawn at 60/120 minutes and 20/30/40 minutes, respectively. Results were compared statistically, and the sensitivity and specificity were determined with receiver-operating characteristic curves.[2] In vivo, caerulein is evaluated in animal models of acute pancreatitis. Mice are treated with caerulein via intraperitoneal injection to induce acute pancreatitis. The severity of pancreatitis is assessed by measuring serum amylase and lipase levels, pancreatic edema, and histopathological changes. The compound's effects on pancreatic secretion are assessed by collecting pancreatic juice. Pharmacokinetic studies are conducted to determine the compound's distribution and metabolism. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Absorbed after intravenous injection. Caerulein (Ceruletide) is a synthetic decapeptide structurally and functionally analogous to cholecystokinin (CCK). It has a molecular formula of C₅₈H₇₃N₁₃O₂₁S₂ and a molecular weight of 1352.4 g/mol. Caerulein is a potent cholecystokinin receptor agonist. It stimulates gastric, biliary, and pancreatic secretion. Caerulein is used as a diagnostic aid in pancreatic malfunction and in paralytic ileus. |
| Toxicity/Toxicokinetics |
The toxicity of caerulein is primarily associated with its ability to induce acute pancreatitis at high doses. In animal studies, caerulein-induced pancreatitis is characterized by edema, inflammation, and acinar cell necrosis. The compound should be used with caution in research involving pancreatic models. Caerulein has been used clinically as a diagnostic aid and has a well-established safety profile at therapeutic doses.
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| References | |
| Additional Infomation |
Pharmacodynamics
Secretin is a specific decapeptide with a function and composition similar to the natural gastrointestinal peptide hormone cholecystokinin, stimulating the secretion of gastric, bile, and pancreatic fluids. It can also stimulate certain smooth muscles. Caerulein (Ceruletide) is a synthetic decapeptide structurally and functionally analogous to cholecystokinin (CCK). It is a potent cholecystokinin receptor agonist. Caerulein stimulates biosynthesis of pancreatic enzymes in AR4-2J pancreatic cells in vitro. It induces acute pancreatitis in mice. Caerulein is used as a diagnostic aid in pancreatic malfunction and in paralytic ileus. |
| Molecular Formula |
C58H73N13O21S2
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|---|---|
| Molecular Weight |
1352.4047
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| Exact Mass |
979.374
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| Elemental Analysis |
C, 51.51; H, 5.44; N, 13.46; O, 24.84; S, 4.74
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| CAS # |
17650-98-5
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| PubChem CID |
16129675
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| Sequence |
{pGlu}-Gln-Asp-Tyr(SO3H)-Thr-Gly-Trp-Met-Asp-Phe-NH2
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| SequenceShortening |
{pGlu}-QD-Y(SO3H)-TGWMDF-NH2
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Melting Point |
224-226° (dec)
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| Index of Refraction |
1.632
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| LogP |
2.46
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| Hydrogen Bond Donor Count |
17
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| Hydrogen Bond Acceptor Count |
22
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| Rotatable Bond Count |
38
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| Heavy Atom Count |
94
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| Complexity |
2840
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| Defined Atom Stereocenter Count |
10
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| SMILES |
S(C([H])([H])[H])C([H])([H])C([H])([H])[C@@]([H])(C(N([H])[C@]([H])(C(N([H])[C@]([H])(C(N([H])[H])=O)C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])=O)C([H])([H])C(=O)O[H])=O)N([H])C([C@]([H])(C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12)N([H])C(C([H])([H])N([H])C([C@]([H])([C@@]([H])(C([H])([H])[H])O[H])N([H])C([C@]([H])(C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])OS(=O)(=O)O[H])N([H])C([C@]([H])(C([H])([H])C(=O)O[H])N([H])C([C@]([H])(C([H])([H])C([H])([H])C(N([H])[H])=O)N([H])C([C@]1([H])C([H])([H])C([H])([H])C(N1[H])=O)=O)=O)=O)=O)=O)=O)=O
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| InChi Key |
YRALAIOMGQZKOW-HYAOXDFASA-N
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| InChi Code |
InChI=1S/C58H73N13O21S2/c1-29(72)49(71-57(87)40(23-31-12-14-33(15-13-31)92-94(89,90)91)68-56(86)43(26-48(78)79)69-52(82)37(16-18-44(59)73)65-51(81)36-17-19-45(74)63-36)58(88)62-28-46(75)64-41(24-32-27-61-35-11-7-6-10-34(32)35)54(84)66-38(20-21-93-2)53(83)70-42(25-47(76)77)55(85)67-39(50(60)80)22-30-8-4-3-5-9-30/h3-15,27,29,36-43,49,61,72H,16-26,28H2,1-2H3,(H2,59,73)(H2,60,80)(H,62,88)(H,63,74)(H,64,75)(H,65,81)(H,66,84)(H,67,85)(H,68,86)(H,69,82)(H,70,83)(H,71,87)(H,76,77)(H,78,79)(H,89,90,91)/t29-,36+,37+,38+,39+,40+,41+,42+,43+,49+/m1/s1
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| Chemical Name |
(3S)-3-[[(2S)-5-amino-5-oxo-2-[[(2S)-5-oxopyrrolidine-2-carbonyl]amino]pentanoyl]amino]-4-[[(2S)-1-[[(2S,3R)-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]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-(4-sulfooxyphenyl)propan-2-yl]amino]-4-oxobutanoic acid
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| Synonyms |
Caerulein; Cerulein; FI-6934; FI 6934; Caerulein; Ceruletide; 17650-98-5; Cerulein; Ceruletida; Ceruletidum; 5-Oxo-L-prolyl-L-glutaminyl-L-alpha-aspartyl-O-sulfo-L-tyrosyl-L-threonylglycyl-L-tryptophyl-L-methionyl-L-alpha-aspartyl-L-phenylalaninamide; 5-Oxo-L-prolyl-L-glutaminyl-L-aspartyl-L-tyrosyl-L-threonylglycyl-L-tryptophyl-L-methionyl-L-aspartylphenyl-L-alaninamide 4-(hydrogen sulfate) (ester); FI6934
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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, avoid exposure to moisture. |
| 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) |
DMSO: ~100 mg/mL (~73.9 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (1.23 mM) (saturation unknown) in 10% DMF 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.67 mg/mL (1.23 mM) (saturation unknown) in 10% DMF 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 1.67 mg/mL (1.23 mM) in 10% DMF 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Solubility in Formulation 4: 5%DMSO + 40%PEG300 + 5%Tween 80 + 50%ddH2O: 2.5mg/ml (1.85mM) Solubility in Formulation 5: 30.3 mg/mL (22.40 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Solubility in Formulation 6: 2 mg/mL (1.48 mM) in Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; Need ultrasonic and adjust pH to 12 with 1M NaOH. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.7394 mL | 3.6971 mL | 7.3942 mL | |
| 5 mM | 0.1479 mL | 0.7394 mL | 1.4788 mL | |
| 10 mM | 0.0739 mL | 0.3697 mL | 0.7394 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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