U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C29H41NO7
Molecular Weight 515.6383
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CANDOXATRIL

SMILES

COCCOC[C@H](CC1(CCCC1)C(=O)N[C@H]2CC[C@H](CC2)C(O)=O)C(=O)OC3=CC=C4CCCC4=C3

InChI

InChIKey=ZTWZVMIYIIVABD-OEMFJLHTSA-N
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

HIDE SMILES / InChI

Molecular Formula C29H41NO7
Molecular Weight 515.6383
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

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
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.
2012-02-29
Role of the effect of inhibition of neutral endopeptidase on vascular and neural complications in streptozotocin-induced diabetic rats.
2011-01-15
Effect of Treatment of Sprague Dawley Rats with AVE7688, Enalapril, or Candoxatril on Diet-Induced Obesity.
2011
New function for an old enzyme: NEP deficient mice develop late-onset obesity.
2010-09-16
The application of fully automated on-line solid phase extraction in bioanalysis.
2010-05-01
Natriuretic and renoprotective effect of chronic oral neutral endopeptidase inhibition in acute renal failure.
2010-01
Inhibition of neutral endopeptidase 24.11 does not potentiate the improvement in glycemic control obtained with dipeptidyl peptidase-4 inhibition in diabetic Goto-Kakizaki rats.
2009-11
Neutral endopeptidase inhibitor suppresses the early phase of atrial electrical remodeling in a canine rapid atrial pacing model.
2008-04-01
Effect of bradykinin metabolism inhibitors on evoked hypotension in rats: rank efficacy of enzymes associated with bradykinin-mediated angioedema.
2008-03
An expanded set of amino acid analogs for the ribosomal translation of unnatural peptides.
2007-10-03
Neutral endopeptidase (EC 3.4.24.11) in cirrhotic liver: a new target to treat portal hypertension?
2005-11
Neutral endopeptidase 24.11 and dipeptidyl peptidase IV are both mediators of the degradation of glucagon-like peptide 1 in the anaesthetised pig.
2005-09
Angiotensin I-converting enzyme-dependent and neutral endopeptidase-dependent generation and degradation of angiotensin II contrarily modulate noradrenaline release: implications for vasopeptidase-inhibitor therapy?
2005-08
Natriuretic and antialdosterone actions of chronic oral NEP inhibition during progressive congestive heart failure.
2005-05
Dual inhibition of angiotensin converting enzyme and neutral endopeptidase produces effective blood pressure control in spontaneously hypertensive rats.
2005
Neutral endopeptidase 24.11 is important for the degradation of both endogenous and exogenous glucagon in anesthetized pigs.
2004-09
Dual inhibition of ACE and NEP provides greater cardioprotection in mice with heart failure.
2004-02
[The new class of drugs-- metalloprotease inhibitors -- in the treatment of heart failure].
2004
Chronic endopeptidase inhibition in DOCA-salt hypertension: mechanism of cardiovascular protection.
2003-08
Potentiation of urinary atrial natriuretic peptide interferes with macula densa function.
2001-08-15
Comparison of a vasopeptidase inhibitor with neutral endopeptidase and angiotensin-converting enzyme inhibitors on bradykinin metabolism in the rat coronary bed.
2001-04
Omapatrilat, a dual angiotensin-converting enzyme and neutral endopeptidase inhibitor, prevents fatty streak deposit in apolipoprotein E-deficient mice.
2001-04
Renal and hormonal effects of chronic inhibition of neutral endopeptidase (EC 3.4.24.11) in normal man.
1993-07
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.
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:11:05 GMT 2025
Edited
by admin
on Mon Mar 31 18:11:05 GMT 2025
Record UNII
ACP75508EE
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
UK-79,300
Preferred Name English
CANDOXATRIL
INN   JAN   MART.   MI   USAN  
INN   USAN  
Official Name English
UK-79300
Code English
CYCLOHEXANECARBOXYLIC ACID, 4-(((1-(3-((2,3-DIHYDRO-1H-INDEN-5-YL)OXY)-2-((2-METHOXYETHOXY)METHYL)-3-OXOPROPYL)CYCLOPENTYL)CARBONYL)AMINO)-, (4(S)-CIS)-
Systematic Name English
CIS-4-(1-(2-(5-INDANYLOXYCARBONYL)-3-(2-METHOXYETHOXY)PROPYL)-1-CYCLOPENTANECARBOXAMIDO)-1-CYCLOHEXANECARBOXYLIC ACID L-
Systematic Name English
(?S)-1-[(cis-4-Carboxycyclohexyl)carbamoyl]-?-[(2-methoxyethoxy)methyl]cyclopentanepropionic acid, ?-5-indanyl ester
Systematic Name English
candoxatril [INN]
Common Name English
CANDOXATRIL [JAN]
Common Name English
CANDOXATRIL [USAN]
Common Name English
CANDOXATRIL [MART.]
Common Name English
CANDOXATRIL [MI]
Common Name English
Code System Code Type Description
SMS_ID
100000081621
Created by admin on Mon Mar 31 18:11:05 GMT 2025 , Edited by admin on Mon Mar 31 18:11:05 GMT 2025
PRIMARY
NCI_THESAURUS
C171870
Created by admin on Mon Mar 31 18:11:05 GMT 2025 , Edited by admin on Mon Mar 31 18:11:05 GMT 2025
PRIMARY
DRUG BANK
DB00616
Created by admin on Mon Mar 31 18:11:05 GMT 2025 , Edited by admin on Mon Mar 31 18:11:05 GMT 2025
PRIMARY
MERCK INDEX
m3015
Created by admin on Mon Mar 31 18:11:05 GMT 2025 , Edited by admin on Mon Mar 31 18:11:05 GMT 2025
PRIMARY Merck Index
CAS
123122-55-4
Created by admin on Mon Mar 31 18:11:05 GMT 2025 , Edited by admin on Mon Mar 31 18:11:05 GMT 2025
PRIMARY
MESH
C062766
Created by admin on Mon Mar 31 18:11:05 GMT 2025 , Edited by admin on Mon Mar 31 18:11:05 GMT 2025
PRIMARY
WIKIPEDIA
CANDOXATRIL
Created by admin on Mon Mar 31 18:11:05 GMT 2025 , Edited by admin on Mon Mar 31 18:11:05 GMT 2025
PRIMARY
EPA CompTox
DTXSID6047286
Created by admin on Mon Mar 31 18:11:05 GMT 2025 , Edited by admin on Mon Mar 31 18:11:05 GMT 2025
PRIMARY
PUBCHEM
5362417
Created by admin on Mon Mar 31 18:11:05 GMT 2025 , Edited by admin on Mon Mar 31 18:11:05 GMT 2025
PRIMARY
USAN
CC-75
Created by admin on Mon Mar 31 18:11:05 GMT 2025 , Edited by admin on Mon Mar 31 18:11:05 GMT 2025
PRIMARY
INN
6558
Created by admin on Mon Mar 31 18:11:05 GMT 2025 , Edited by admin on Mon Mar 31 18:11:05 GMT 2025
PRIMARY
ChEMBL
CHEMBL35084
Created by admin on Mon Mar 31 18:11:05 GMT 2025 , Edited by admin on Mon Mar 31 18:11:05 GMT 2025
PRIMARY
CHEBI
3353
Created by admin on Mon Mar 31 18:11:05 GMT 2025 , Edited by admin on Mon Mar 31 18:11:05 GMT 2025
PRIMARY
FDA UNII
ACP75508EE
Created by admin on Mon Mar 31 18:11:05 GMT 2025 , Edited by admin on Mon Mar 31 18:11:05 GMT 2025
PRIMARY
EVMPD
SUB06072MIG
Created by admin on Mon Mar 31 18:11:05 GMT 2025 , Edited by admin on Mon Mar 31 18:11:05 GMT 2025
PRIMARY
Related Record Type Details
ACTIVE MOIETY