Ceruletide

• CAT Number: I002295
• CAS Number: 17650-98-5
• Purity: ≥95%
• Synonyms: (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
• InChI: 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
• InChIKey: YRALAIOMGQZKOW-HYAOXDFASA-N
• SMILES: CC(C(C(=O)NCC(=O)NC(CC1=CNC2=CC=CC=C21)C(=O)NC(CCSC)C(=O)NC(CC(=O)O)C(=O)NC(CC3=CC=CC=C3)C(=O)N)NC(=O)C(CC4=CC=C(C=C4)OS(=O)(=O)O)NC(=O)C(CC(=O)O)NC(=O)C(CCC(=O)N)NC(=O)C5CCC(=O)N5)O

Ceruletide is a decapeptide and a potent cholecystokinin receptor agonist. Ceruletide is a safe and effective cholecystokinetic agent with a direct spasmogenic effect on the gallbladder muscle and bile ducts[1].
Ceruletide is similar chemically and biologically to the human gastrointestinal hormones cholecystokinin-pancreozymin (CCK) and gastrin II. Ceruletide stimulates gallbladder contraction, pancreatic exocrine secretion, gastric secretion, and motility in the distal duodenum, jejunum, ileum and colon, while delaying gastric emptying and inhibiting motility in the proximal duodenum[1]. Ceruletide in supramaximal but not in physiological doses activates NF-kappaB/Rel in vitro. This activation may induce a self-defending genetic program before the onset of cellular injury, which may prevent higher degrees of damage of pancreatic acinar cells after secretagogue hyperstimulation[2].
CeruLetide (0.4-0.5 μg/kg, IV; 3-4 μg/kg, SC) causes vomiting and defecation in conscious intact dogs 15-30 minutes after IV injection and 2-4 hours after full recovery after sc administration . CeruLetide (5-15 ng/kg, iv) exhibits significant spasmogenic effects on the pylorus in rats. CeruLetide also reduces blood pressure 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 portosystemic shunts (PSS) and is more sensitive for detecting liver dysfunction in dogs with upper respiratory disease (URD)[3 ].When S35-labeled Ceruletide is injected intramuscularly in rats, rabbits and mice, radioactivity in the blood reached a maximum at 5 and 15 min in rats and rabbits respec tively and then decreased rapidly. And the acute toxicity studies in mice show an i.v. LD50 of 1012 mg/kg[4].
Ceruletide-induced pancreatitis is a great characterized animal models of pancreatitis, which is highly reproducible and economical. It has been widely used to generate both acute and chronic pancreatitis in mice and rats[5].
1. Induction of Acute Pancreatitis[6][7][8]
Background

Ceruletide acts on CCK receptors, which are often expressed on various species of pancreatic acinar cells. Ceruletide induces dysregulation of the production and secretion of digestive enzymes, leading to cytoplasmic vacuolization and the death of acinar cells, edema formation, and an infiltration of inflammatory cells into the pancreas.
Specific Mmodeling Methods

1. Mice: C57Bl/6n mice • 8-12 week-old
Administration: Ceruletide 50 μg/kg • i.p. • 8 hourly, total 8 times;
2. Mice: C57BL6/J mice • male • 6-8 week-old
Administration: Ceruletide 100?μg/kg plus LPS (5?mg/kg, i.p. immediately after the last injection of Ceruletide) • i.p. • 10 hourly, total 10 times;
or Ceruletide (50 μg/kg, 7 hourly, total 7 times) plus LPS (10 mg/kg, once) • i.p.

Note

(1) Cerulein induces rapid pancreatitis and rapid spontaneous recovery within one week in mammals. Therefore, mice are usually euthanized within 24?h after the first Ceruletide injection.
Modeling Indicators

Molecular changes: Increased serum amylase, serum lipase, TNF-α, and IL-1β level.
Histology analysis: Pancreatic edema, inflammatory infiltration, and acinar cell necrosis (H&E staining).
Correlated Product(s): Lipopolysaccharides
(HY-D1056)
Opposite Product(s):