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Identification
NameCeruletide
Accession NumberDB00403  (APRD00861)
TypeSmall Molecule
GroupsApproved
Description

Caerulein is a specific decapeptide similar in action and composition to the natural gastrointestinal peptide hormone cholecystokinin. It stimulates gastric, biliary, and pancreatic secretion; and certain smooth muscle.

Structure
Thumb
Synonyms
SynonymLanguageCode
CaeruleinNot AvailableNot Available
CeruleinNot AvailableNot Available
CeruletidaNot AvailableNot Available
CeruletidumNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
TakusPfizer
Brand mixturesNot Available
Categories
CAS number17650-98-5
WeightAverage: 1352.405
Monoisotopic: 1351.448537843
Chemical FormulaC58H73N13O21S2
InChI KeyYRALAIOMGQZKOW-HYAOXDFASA-N
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
IUPAC Name
(3S)-3-{[(1S)-1-carbamoyl-2-phenylethyl]carbamoyl}-3-[(2S)-2-[(2S)-2-{2-[(2S,3R)-2-[(2S)-2-[(2S)-2-[(2S)-4-carbamoyl-2-{[(2S)-5-oxopyrrolidin-2-yl]formamido}butanamido]-3-carboxypropanamido]-3-[4-(sulfooxy)phenyl]propanamido]-3-hydroxybutanamido]acetamido}-3-(1H-indol-3-yl)propanamido]-4-(methylsulfanyl)butanamido]propanoic acid
SMILES
[H][C@](NC(=O)[C@H](CC1=CC=C(OS(O)(=O)=O)C=C1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCC(=O)N1)([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC1=CNC2=CC=CC=C12)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(N)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptidomimetics
Alternative parentsN-acyl-alpha Amino Acids and Derivatives; Tryptamines and Derivatives; Alpha Amino Acid Amides; Phenylsulfates; Beta Amino Acids and Derivatives; Phenylpropylamines; Amphetamines and Derivatives; Indoles; Pyrrolidinecarboxamides; Amino Fatty Acids; Dicarboxylic Acids and Derivatives; Sulfuric Acid Monoesters; Pyrrolidones; Substituted Pyrroles; Lactams; Secondary Alcohols; Primary Carboxylic Acid Amides; Polyols; Secondary Carboxylic Acid Amides; Carboxylic Acids; Polyamines; Enolates; Thioethers
Substituentsn-acyl-alpha amino acid or derivative; alpha-amino acid amide; triptan; tryptamine; beta amino acid or derivative; phenylsulfate; amphetamine or derivative; phenylpropylamine; alpha-amino acid or derivative; indole; indole or derivative; pyrrolidine carboxylic acid or derivative; pyrrolidine-2-carboxamide; sulfuric acid monoester; benzene; dicarboxylic acid derivative; sulfate-ester; pyrrolidone; substituted pyrrole; pyrrole; sulfuric acid derivative; pyrrolidine; secondary alcohol; primary carboxylic acid amide; lactam; carboxamide group; polyol; secondary carboxylic acid amide; polyamine; enolate; thioether; carboxylic acid; amine; organonitrogen compound; alcohol
Classification descriptionThis compound belongs to the peptidomimetics. These are compounds containing non-peptidic structural elements that is capable of mimicking or antagonizing the biological action(s) of a natural parent peptide.
Pharmacology
IndicationCaerulein stimulates gastric, biliary, and pancreatic secretion; and certain smooth muscle. As such, it is used in paralytic ileus and as diagnostic aid in pancreatic malfunction.
PharmacodynamicsCaerulein is a specific decapeptide similar in action and composition to the natural gastrointestinal peptide hormone cholecystokinin. It stimulates gastric, biliary, and pancreatic secretion; and certain smooth muscle.
Mechanism of actionCaerulein acts according to its similarity to the natural gastrointestinal peptide hormone cholecystokinin. Cholecystokinin is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein. Cholecystokinin is secreted by the duodenum, the first segment of the small intestine. There it binds to CCK receptors, activating them and causing downstream effects. Specifically, it results in the release of digestive enzymes and bile from the pancreas and gall bladder, respectively. It also acts as a hunger suppresant. Cholecystokinin is secreted by the duodenum when fat- or protein-rich chyme leaves the stomach and enters the duodenum. The hormone acts on the pancreas to stimulate the secretion of the enzymes lipase, amylase, trypsin, and chymotrypsin. Together these pancreatic enzymes catalyze the digestion of fat and protein. Cholecystokinin also stimulates both the contraction of the gall bladder, and the relaxtion of the Sphincter of Oddi (Glisson's Sphinctor), which delivers, (not secretes) bile into the small intestine. Bile salts serve to emulsify fats, thereby increasing the effectiveness with which enzymes can digest them.
AbsorptionAbsorbed following intravenous administration.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.8428
Blood Brain Barrier - 0.7051
Caco-2 permeable - 0.7114
P-glycoprotein substrate Substrate 0.7616
P-glycoprotein inhibitor I Non-inhibitor 0.8646
P-glycoprotein inhibitor II Non-inhibitor 0.9946
Renal organic cation transporter Non-inhibitor 0.8644
CYP450 2C9 substrate Non-substrate 0.8617
CYP450 2D6 substrate Non-substrate 0.7832
CYP450 3A4 substrate Substrate 0.5706
CYP450 1A2 substrate Non-inhibitor 0.7836
CYP450 2C9 substrate Non-inhibitor 0.7725
CYP450 2D6 substrate Non-inhibitor 0.8592
CYP450 2C19 substrate Non-inhibitor 0.7546
CYP450 3A4 substrate Non-inhibitor 0.9364
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8493
Ames test Non AMES toxic 0.6179
Carcinogenicity Non-carcinogens 0.6434
Biodegradation Not ready biodegradable 0.9879
Rat acute toxicity 2.6037 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8006
hERG inhibition (predictor II) Inhibitor 0.5939
Pharmacoeconomics
Manufacturers
  • Pharmacia and upjohn co
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP-0.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0116ALOGPS
logP-0.19ALOGPS
logP-5.2ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)-2ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count20ChemAxon
Hydrogen Donor Count17ChemAxon
Polar Surface Area551.4 Å2ChemAxon
Rotatable Bond Count38ChemAxon
Refractivity325.74 m3·mol-1ChemAxon
Polarizability129.96 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Bernardi, L., Bosisio, G., De Castiglione, R. and Goffredo, O. ;U.S. Patent 3,472,832; Oct. 14,
1969; assigned to Societa Farmaceutici ltalia (Italy).

General ReferenceNot Available
External Links
ResourceLink
ChEBI59219
ChEMBLCHEMBL1201355
Therapeutic Targets DatabaseDAP000961
PharmGKBPA164774919
ATC CodesV04CC04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Cholecystokinin receptor type A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inducer

Components

Name UniProt ID Details
Cholecystokinin receptor type A P32238 Details

References:

  1. Ishikawa Y, Shimatsu A, Murakami Y, Imura H: Barrel rotation in rats induced by SMS 201-995: suppression by ceruletide. Pharmacol Biochem Behav. 1990 Nov;37(3):523-6. Pubmed
  2. Katsuura G, Ibii N, Matsushita A: Activation of CCK-A receptors induces elevation of plasma corticosterone in rats. Peptides. 1992 Jan-Feb;13(1):203-5. Pubmed
  3. Maurice T, Hiramatsu M, Kameyama T, Hasegawa T, Nabeshima T: Cholecystokinin-related peptides, after systemic or central administration, prevent carbon monoxide-induced amnesia in mice. J Pharmacol Exp Ther. 1994 May;269(2):665-73. Pubmed
  4. Shinohara S, Katsuura G, Eigyo M, Shintaku H, Ibii N, Matsushita A: Inhibitory effect of CCK-8 and ceruletide on glutamate-induced rises in intracellular free calcium concentrations in rat neuron cultures. Brain Res. 1992 Aug 21;588(2):223-8. Pubmed
  5. Ibii N, Ikeda M, Takahara Y, Eigyo M, Akiyoshi T, Matsushita A: Inhibitory effect of ceruletide on haloperidol-induced catalepsy in rats. Peptides. 1989 Jul-Aug;10(4):779-83. Pubmed
  6. Makovec F, Bani M, Cereda R, Chiste R, Pacini MA, Revel L, Rovati LA, Rovati LC, Setnikar I: Pharmacological properties of lorglumide as a member of a new class of cholecystokinin antagonists. Arzneimittelforschung. 1987 Nov;37(11):1265-8. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 03, 2014 14:21