Identification

Name
Bentiromide
Accession Number
DB00522  (APRD00818)
Type
Small Molecule
Groups
Investigational, Withdrawn
Description

Bentiromide is a peptide used as a screening test for exocrine pancreatic insufficiency and to monitor the adequacy of supplemental pancreatic therapy. It is given by mouth as a noninvasive test. The amount of 4-aminobenzoic acid and its metabolites excreted in the urine is taken as a measure of the chymotrypsin-secreting activity of the pancreas. Headache and gastrointestinal disturbances have been reported in patients taking bentiromide. Bentiromide is not available in the U.S. or Canada (It was withdrawn in the US in October 1996).

Structure
Thumb
Synonyms
  • Bentiromide
  • Bentiromido
  • Bentiromidum
  • BTPABA
  • PFT
External IDs
E 2663 / E-2663 / Ro 11-7891
International/Other Brands
PFD (Sannova)
Categories
UNII
239IF5W61J
CAS number
37106-97-1
Weight
Average: 404.4153
Monoisotopic: 404.13722176
Chemical Formula
C23H20N2O5
InChI Key
SPPTWHFVYKCNNK-FQEVSTJZSA-N
InChI
InChI=1S/C23H20N2O5/c26-19-12-6-15(7-13-19)14-20(25-21(27)16-4-2-1-3-5-16)22(28)24-18-10-8-17(9-11-18)23(29)30/h1-13,20,26H,14H2,(H,24,28)(H,25,27)(H,29,30)/t20-/m0/s1
IUPAC Name
4-[(2S)-3-(4-hydroxyphenyl)-2-(phenylformamido)propanamido]benzoic acid
SMILES
OC(=O)C1=CC=C(NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)C2=CC=CC=C2)C=C1

Pharmacology

Indication

Used as a screening test for exocrine pancreatic insufficiency and to monitor the adequacy of supplemental pancreatic therapy.

Pharmacodynamics

Bentiromide is a peptide used as a screening test for exocrine pancreatic insufficiency and to monitor the adequacy of supplemental pancreatic therapy. It is given by mouth as a noninvasive test. The amount of p-aminobenzoic acid and its metabolites excreted in the urine is taken as a measure of the chymotrypsin-secreting activity of the pancreas. Headache and gastrointestinal disturbances have been reported in patients taking bentiromide. Bentiromide is not available in the U.S. or Canada.

Mechanism of action

Bentiromide is a peptide that is broken down in the pancreas by chymotrypsin. By determining the output of unchanged bentiromide in the urine following oral administration, it is possible to determine the sufficiency of pancreatic activity.

TargetActionsOrganism
ASerine protease hepsin
ligand
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Primarily hepatic. Enzymatic activity capable of hydrolyzing bentiromide has also been found in normal small intestine.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Symptoms of overdose include shortness of breath and troubled breathing.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

DeBenneville, P.L.and Greenberger, N.J.; U.S. Patent 3,745,212; July 10,1973; assigned to Rohm & Haas Co.

General References
  1. Toskes PP: The bentiromide test for pancreatic exocrine insufficiency. Pharmacotherapy. 1984 Mar-Apr;4(2):74-80. [PubMed:6371722]
External Links
Human Metabolome Database
HMDB0014663
KEGG Drug
D01346
PubChem Compound
6957673
PubChem Substance
46508175
ChemSpider
5329364
ChEBI
31263
ChEMBL
CHEMBL1200368
PharmGKB
PA164750572
Wikipedia
Bentiromide
ATC Codes
V04CK03 — Bentiromide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2RecruitingTreatmentAcne Vulgaris Superficial Mixed Comedonal and Inflammatory1
2RecruitingTreatmentInterstitial Lung Disease (ILD) / Scleroderma, Systemic1

Pharmacoeconomics

Manufacturers
  • Savage laboratories inc div altana inc
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)240-242DeBenneville, P.L.and Greenberger, N.J.; U.S. Patent 3,745,212; July 10,1973; assigned to Rohm & Haas Co.
logP3.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00412 mg/mLALOGPS
logP2.99ALOGPS
logP3.54ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)4.16ChemAxon
pKa (Strongest Basic)-1.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area115.73 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity112.74 m3·mol-1ChemAxon
Polarizability42.16 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.5224
Blood Brain Barrier+0.7085
Caco-2 permeable-0.7954
P-glycoprotein substrateNon-substrate0.5201
P-glycoprotein inhibitor INon-inhibitor0.9668
P-glycoprotein inhibitor IINon-inhibitor0.9765
Renal organic cation transporterNon-inhibitor0.9466
CYP450 2C9 substrateNon-substrate0.7866
CYP450 2D6 substrateNon-substrate0.8148
CYP450 3A4 substrateNon-substrate0.6344
CYP450 1A2 substrateNon-inhibitor0.8856
CYP450 2C9 inhibitorNon-inhibitor0.7744
CYP450 2D6 inhibitorNon-inhibitor0.9233
CYP450 2C19 inhibitorNon-inhibitor0.8775
CYP450 3A4 inhibitorNon-inhibitor0.9168
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9014
Ames testNon AMES toxic0.9317
CarcinogenicityNon-carcinogens0.8637
BiodegradationNot ready biodegradable0.7682
Rat acute toxicity1.8601 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9831
hERG inhibition (predictor II)Non-inhibitor0.9543
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as tyrosine and derivatives. These are compounds containing tyrosine or a derivative thereof resulting from reaction of tyrosine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Tyrosine and derivatives
Alternative Parents
Phenylalanine and derivatives / Acylaminobenzoic acid and derivatives / Hippuric acids and derivatives / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Amphetamines and derivatives / Anilides / Benzoic acids / N-arylamides / Benzoyl derivatives
show 9 more
Substituents
Tyrosine or derivatives / Phenylalanine or derivatives / Hippuric acid or derivatives / N-acyl-alpha amino acid or derivatives / Acylaminobenzoic acid or derivatives / Alpha-amino acid amide / Amphetamine or derivatives / Benzoic acid or derivatives / Anilide / Benzoic acid
show 22 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
dipeptide (CHEBI:31263)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Ligand
General Function
Serine-type peptidase activity
Specific Function
Plays an essential role in cell growth and maintenance of cell morphology. May mediate the activating cleavage of HGF and MST1/HGFL. Plays a role in the proteolytic processing of ACE2.
Gene Name
HPN
Uniprot ID
P05981
Uniprot Name
Serine protease hepsin
Molecular Weight
45011.01 Da
References
  1. Chowdhury RS, Forsmark CE: Review article: Pancreatic function testing. Aliment Pharmacol Ther. 2003 Mar 15;17(6):733-50. [PubMed:12641496]
  2. Bujanover Y, Harel A, Geter R, Blau H, Yahav J, Spirer Z: The development of the chymotryptic activity during postnatal life using the bentiromide test. Int J Pancreatol. 1988 Jan-Feb;3(1):53-8. [PubMed:3258344]
  3. Toskes PP: The bentiromide test for pancreatic exocrine insufficiency. Pharmacotherapy. 1984 Mar-Apr;4(2):74-80. [PubMed:6371722]
  4. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 04:45