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Details

Stereochemistry ABSOLUTE
Molecular Formula C20H33NO7
Molecular Weight 399.4785
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CANDOXATRILAT

SMILES

COCCOC[C@H](CC1(CCCC1)C(=O)N[C@H]2CC[C@H](CC2)C(O)=O)C(O)=O

InChI

InChIKey=ACZWIDANLCXHBM-HRCADAONSA-N
InChI=1S/C20H33NO7/c1-27-10-11-28-13-15(18(24)25)12-20(8-2-3-9-20)19(26)21-16-6-4-14(5-7-16)17(22)23/h14-16H,2-13H2,1H3,(H,21,26)(H,22,23)(H,24,25)/t14-,15-,16+/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/1315825 | https://www.ncbi.nlm.nih.gov/pubmed/10937982 | https://www.ncbi.nlm.nih.gov/pubmed/21515054 | https://www.ncbi.nlm.nih.gov/pubmed/2529858 | https://www.ncbi.nlm.nih.gov/pubmed/26082640

Candoxatril is the orally-active prodrug of candoxatrilat (UK-73967), a potent neutral endopeptidase (NEP) inhibitor. 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. Candoxatril is the first drug of its kind to be released for clinical trials regarding heart failure. This is because Candoxatril produces favorable hemodynamic effects in patients with chronic heart failure. It has been demonstrated that Candoxatril is associated with a beneficial hemodynamic effect that is useful both for rest and exercise. In several different studies, candoxatril has been shown to improve performance in people with heart failure. In one study, 12 different patients were selected, all with moderately severe heart failure. On day one of this study, the candoxatril had increased plasma ANP levels, suppressed aldosterone and decreased right atrial and pulmonary capillary wedge pressures. After treatment for 10 days, patients health had improved with an increase of basal ANP and a decrease of aldosterone, along with a reduced body weight that could be a reflection of chronic natriuretic, diuretic effects, or both. It was decided that on day 10 of the study, the effects of candoxatril were similar to that on day one.

Originator

Curator's Comment: # Pfizer Central Research

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
7.8 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Renal and hormonal effects of chronic inhibition of neutral endopeptidase (EC 3.4.24.11) in normal man.
1993 Jul
[The new class of drugs-- metalloprotease inhibitors -- in the treatment of heart failure].
2004
Dual inhibition of angiotensin converting enzyme and neutral endopeptidase produces effective blood pressure control in spontaneously hypertensive rats.
2005
Natriuretic and antialdosterone actions of chronic oral NEP inhibition during progressive congestive heart failure.
2005 May
Effect of Treatment of Sprague Dawley Rats with AVE7688, Enalapril, or Candoxatril on Diet-Induced Obesity.
2011
Effect of inhibition of angiotensin converting enzyme and/or neutral endopeptidase on vascular and neural complications in high fat fed/low dose streptozotocin-diabetic rats.
2012 Feb 29
Patents

Patents

Sample Use Guides

200 mg candoxatril capsules twice daily.
Route of Administration: Oral
In Vitro Use Guide
The acute effect of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) on pulmonary vascular tone in normoxia and acute hypoxia in the absence and presence of a specific inhibitor of neutral endopeptidase 24.11 (NEI, UK 73, 967, candoxatrilat; Pfizer) in the isolated and blood-perfused rat lung preparation was studied. Baseline pulmonary artery pressure (Ppa) was 16.4 +/- 0.3 mm Hg in lungs from normoxic control rats and 22.5 +/- 0.3 mm Hg in lungs from rats kept in hypoxia (FIO2 = 10%) for 7 days. Acute hypoxic pulmonary vasoconstriction (HPV delta Ppa) was similar in normoxic control rats (9.5 +/- 0.6 mm Hg) and chronically hypoxic rats (9.8 +/- 0.9 mm Hg). NEI at 0.07 and 0.2 mg had no effect on baseline Ppa or HPV delta Ppa. Synthetic BNP at 10 nM had no effect on baseline Ppa but produced a 2.8 +/- 0.2 mm Hg reduction in HPV delta Ppa alone and 2.7 +/- 0.2 mm Hg reduction in the presence of 0.07 mg NEI in normoxic control rats. In contrast, ANP at 10 nM produced a significantly greater decrease in HPV delta Ppa in the presence of 0.07 mg NEI (4.8 +/- 0.3 mm Hg, p < 0.05) compared with ANP alone (2.9 +/- 0.4 mm Hg), and similar results were also observed in chronically hypoxic rats.
Name Type Language
CANDOXATRILAT
INN   USAN  
INN   USAN  
Official Name English
CANDOXATRIL DIACID
MI  
Preferred Name English
candoxatrilat [INN]
Common Name English
UK-73,967
Code English
UK-73967
Code English
CANDOXATRILAT [USAN]
Common Name English
(?S)-1-[(cis-4-Carboxycyclohexyl)carbamoyl]-?-[(2-methoxyethoxy)methyl]cyclopentanepropionic acid
Systematic Name English
CANDOXATRIL DIACID [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C783
Created by admin on Mon Mar 31 18:19:01 GMT 2025 , Edited by admin on Mon Mar 31 18:19:01 GMT 2025
Code System Code Type Description
MERCK INDEX
m3015
Created by admin on Mon Mar 31 18:19:01 GMT 2025 , Edited by admin on Mon Mar 31 18:19:01 GMT 2025
PRIMARY Merck Index
NCI_THESAURUS
C77602
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PRIMARY
CAS
123122-54-3
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PRIMARY
DRUG BANK
DB11623
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PRIMARY
USAN
CC-74
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PRIMARY
CHEBI
3354
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PRIMARY
SMS_ID
100000081602
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PRIMARY
ChEMBL
CHEMBL434492
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PRIMARY
FDA UNII
7WU8BZ90TH
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PRIMARY
EPA CompTox
DTXSID001014436
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PRIMARY
PUBCHEM
443380
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PRIMARY
INN
6557
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PRIMARY
EVMPD
SUB06073MIG
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PRIMARY
WIKIPEDIA
Candoxatrilat
Created by admin on Mon Mar 31 18:19:01 GMT 2025 , Edited by admin on Mon Mar 31 18:19:01 GMT 2025
PRIMARY
MESH
C060942
Created by admin on Mon Mar 31 18:19:01 GMT 2025 , Edited by admin on Mon Mar 31 18:19:01 GMT 2025
PRIMARY