NAV

Candoxatril

Identification

Generic Name
Candoxatril
DrugBank Accession Number
DB00616
Background

Candoxatril is the orally-active prodrug of candoxatrilat (UK-73967), a potent neutral endopeptidase (NEP) inhibitor.

Type
Small Molecule
Groups
Experimental
Structure
Similar Structures
Weight
Average: 515.6383
Monoisotopic: 515.288302671
Chemical Formula
C29H41NO7
Synonyms
  • [4(S)-cis]-4-[[[1-[3-[(2,3-dihydro-1H-Indeb5-yl)oxy]-2-[(2-methoxyethoxy)methyl]-3-oxopropyl]cyclopentyl]carbonyl]amino]cyclohexanecarboxylic acid
  • 4-({1-[(S)-2-(indan-5-yloxycarbonyl)-3-(2-methoxy-ethoxy)-propyl]-cyclopentanecarbonyl}-amino)-cyclohexanecarboxylic acid
  • Candoxatril
External IDs
  • UK-79,300
  • UK-79300
Poor quality drug data slowing you down?
Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.
Download eBook
Poor quality drug data slowing you down?
Download eBook

Pharmacology

Indication

Not Available

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Not Available

Mechanism of action

Neutral endopeptidase inhibitors such as Candoxatril have a dual mechanism of action. They inhibit two metalloprotease enzymes, neutral endopeptidase and ACE, resulting in an increased availability of natriuretic peptides that exhibit vasodilatory effects and, possibly, tissue protective effects.

TargetActionsOrganism
ANeprilysin
inhibitor
Humans
UAngiotensin-converting enzyme
inhibitor
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
Integrate drug-drug
interactions in your software
AbaloparatideAbaloparatide may increase the hypotensive activities of Candoxatril.
AcebutololCandoxatril may increase the hypotensive activities of Acebutolol.
AceclofenacThe therapeutic efficacy of Candoxatril can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Candoxatril can be decreased when used in combination with Acemetacin.
Acetylsalicylic acidAcetylsalicylic acid may decrease the antihypertensive activities of Candoxatril.
Food Interactions
Not Available

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Active Moieties
NameKindUNIICASInChI Key
Candoxatrilatprodrug7WU8BZ90TH123122-54-3ACZWIDANLCXHBM-HRCADAONSA-N

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as indanes. These are compounds containing an indane moiety, which consists of a cyclopentane fused to a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Indanes
Sub Class
Not Available
Direct Parent
Indanes
Alternative Parents
Fatty acid esters / Fatty amides / Dicarboxylic acids and derivatives / Secondary carboxylic acid amides / Carboxylic acid esters / Dialkyl ethers / Carboxylic acids / Organopnictogen compounds / Organonitrogen compounds / Organic oxides
show 2 more
Substituents
Aromatic homopolycyclic compound / Carbonyl group / Carboxamide group / Carboxylic acid / Carboxylic acid derivative / Carboxylic acid ester / Dialkyl ether / Dicarboxylic acid or derivatives / Ether / Fatty acid ester
show 11 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
dicarboxylic acid monoester, monocarboxylic acid, monocarboxylic acid amide (CHEBI:3353)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
ACP75508EE
CAS number
123122-55-4
InChI Key
ZTWZVMIYIIVABD-OEMFJLHTSA-N
InChI
InChI=1S/C29H41NO7/c1-35-15-16-36-19-23(27(33)37-25-12-9-20-5-4-6-22(20)17-25)18-29(13-2-3-14-29)28(34)30-24-10-7-21(8-11-24)26(31)32/h9,12,17,21,23-24H,2-8,10-11,13-16,18-19H2,1H3,(H,30,34)(H,31,32)/t21-,23-,24+/m0/s1
IUPAC Name
(1s,4s)-4-{1-[(2S)-3-(2,3-dihydro-1H-inden-5-yloxy)-2-[(2-methoxyethoxy)methyl]-3-oxopropyl]cyclopentaneamido}cyclohexane-1-carboxylic acid
SMILES
COCCOC[C@H](CC1(CCCC1)C(=O)N[C@H]1CC[C@H](CC1)C(O)=O)C(=O)OC1=CC2=C(CCC2)C=C1

References

General References
Not Available
Human Metabolome Database
HMDB0014754
KEGG Drug
D01070
PubChem Compound
5362417
PubChem Substance
46509011
ChemSpider
16736409
BindingDB
50084625
ChEBI
3353
ChEMBL
CHEMBL35084
Therapeutic Targets Database
DAP001145
PharmGKB
PA164764517
Wikipedia
Candoxatril

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP3.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00225 mg/mLALOGPS
logP3.55ALOGPS
logP4.68Chemaxon
logS-5.4ALOGPS
pKa (Strongest Acidic)4.29Chemaxon
pKa (Strongest Basic)0.48Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area111.16 Å2Chemaxon
Rotatable Bond Count13Chemaxon
Refractivity138.16 m3·mol-1Chemaxon
Polarizability57.31 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9142
Blood Brain Barrier+0.8437
Caco-2 permeable-0.6787
P-glycoprotein substrateSubstrate0.8158
P-glycoprotein inhibitor INon-inhibitor0.8213
P-glycoprotein inhibitor IINon-inhibitor0.9075
Renal organic cation transporterNon-inhibitor0.7707
CYP450 2C9 substrateNon-substrate0.7497
CYP450 2D6 substrateNon-substrate0.7492
CYP450 3A4 substrateSubstrate0.6952
CYP450 1A2 substrateNon-inhibitor0.7035
CYP450 2C9 inhibitorNon-inhibitor0.7548
CYP450 2D6 inhibitorNon-inhibitor0.8484
CYP450 2C19 inhibitorNon-inhibitor0.6641
CYP450 3A4 inhibitorNon-inhibitor0.9144
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8421
Ames testNon AMES toxic0.62
CarcinogenicityNon-carcinogens0.9494
BiodegradationNot ready biodegradable0.8614
Rat acute toxicity2.5001 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9833
hERG inhibition (predictor II)Non-inhibitor0.5652
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-MSsplash10-001i-8903400000-268da98bf001b2697ad3
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-014j-0022930000-183505fa9a778fdb485a
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-08fs-0281910000-9e5567ee3a45217f8d7f
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-000f-1933100000-845e25536b928f7492a0
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-6557890000-438980c731d2f70805ab
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-01ox-9584320000-6752be6205def34db63d
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-014r-6766590000-cf2570d6d85f42d7e337
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-240.8726267
predicted
DarkChem Lite v0.1.0
[M-H]-234.8494529
predicted
DarkChem Lite v0.1.0
[M-H]-243.0039267
predicted
DarkChem Lite v0.1.0
[M-H]-219.588
predicted
DeepCCS 1.0 (2019)
[M+H]+241.6071267
predicted
DarkChem Lite v0.1.0
[M+H]+218.8083499
predicted
DarkChem Lite v0.1.0
[M+H]+241.0544267
predicted
DarkChem Lite v0.1.0
[M+H]+221.98357
predicted
DeepCCS 1.0 (2019)
[M+Na]+241.6005267
predicted
DarkChem Lite v0.1.0
[M+Na]+225.4130144
predicted
DarkChem Lite v0.1.0
[M+Na]+241.5345267
predicted
DarkChem Lite v0.1.0
[M+Na]+227.94556
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details1. Neprilysin
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:8168535). Biologically important in the destruction of opioid peptide...
Gene Name
MME
Uniprot ID
P08473
Uniprot Name
Neprilysin
Molecular Weight
85513.225 Da
References
  1. O'Connell JE, Jardine AG, Davidson G, Connell JM: Candoxatril, an orally active neutral endopeptidase inhibitor, raises plasma atrial natriuretic factor and is natriuretic in essential hypertension. J Hypertens. 1992 Mar;10(3):271-7. [Article]
  2. Elsner D, Muntze A, Kromer EP, Riegger GA: Effectiveness of endopeptidase inhibition (candoxatril) in congestive heart failure. Am J Cardiol. 1992 Aug 15;70(4):494-8. [Article]
  3. Plamboeck A, Holst JJ, Carr RD, Deacon CF: Neutral endopeptidase 24.11 and dipeptidyl peptidase IV are both mediators of the degradation of glucagon-like peptide 1 in the anaesthetised pig. Diabetologia. 2005 Sep;48(9):1882-90. Epub 2005 Jul 16. [Article]
  4. Sansoe G, Aragno M, Mastrocola R, Cutrin JC, Silvano S, Mengozzi G, Smedile A, Rosina F, Danni O, Rizzetto M: Overexpression of kidney neutral endopeptidase (EC 3.4.24.11) and renal function in experimental cirrhosis. Am J Physiol Renal Physiol. 2006 Jun;290(6):F1337-43. Epub 2006 Jan 31. [Article]
  5. Hirata Y, Suzuki E, Hayakawa H, Matsuoka H, Sugimoto T, Kangawa K, Matsuo H: Mechanisms of the natriuretic effects of neutral endopeptidase inhibition in Dahl salt-sensitive and salt-resistant rats. J Cardiovasc Pharmacol. 1994 Feb;23(2):283-90. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Details2. Angiotensin-converting enzyme
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent...
Gene Name
ACE
Uniprot ID
P12821
Uniprot Name
Angiotensin-converting enzyme
Molecular Weight
149713.675 Da
References
  1. Dumoulin MJ, Adam A, Rouleau JL, Lamontagne D: Comparison of a vasopeptidase inhibitor with neutral endopeptidase and angiotensin-converting enzyme inhibitors on bradykinin metabolism in the rat coronary bed. J Cardiovasc Pharmacol. 2001 Apr;37(4):359-66. [Article]
  2. Kostova E, Jovanoska E, Zafirov D, Jakovski K, Maleska V, Slaninka-Miceska M: Dual inhibition of angiotensin converting enzyme and neutral endopeptidase produces effective blood pressure control in spontaneously hypertensive rats. Bratisl Lek Listy. 2005;106(12):407-11. [Article]

Drug created at June 13, 2005 13:24 / Updated at December 02, 2023 06:53