DT-Web

DB00616 - Candoxatril


Identification
Name Candoxatril
Accession Number DB00616 (APRD00027)
Type small molecule
Description Candoxatril is the orally-active prodrug of candoxatrilat (UK-73967), the active enantiomer of candoxatrilat (UK-69578), a potent neutral endopeptidase (NEP) inhibitor used in the treatment of chronic heart failure.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 515.6383
Groups approved
Monoisotopic Weight 515.288302671
Pharmacology
Indication For treatment of hypertension, improve exercise capacity in patients with CHF receiving angiotensin converting enzyme inhibition.
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.
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Neprilysin
Name Neprilysin
Gene Name MME
Pharmacological action yes
Actions inhibitor
References
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.3751
Angiotensin-converting enzyme
Name Angiotensin-converting enzyme
Gene Name ACE
Pharmacological action unknown
Actions inhibitor
References
  • 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. - Pubmed
  • 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. - Pubmed
DTHybrid score 0.542

Predictions


Id Partner name Gene Name Score
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.1789
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.1375
957 Glucagon-like peptide 1 receptor GLP1R 0.0863
3060 Leukotriene A-4 hydrolase LTA4H 0.0863
6285 Thermolysin npr 0.0648
2457 Bacillolysin nprS 0.0635
1385 Angiotensin-converting enzyme 2 ACE2 0.0605
952 Dipeptidyl peptidase 4 DPP4 0.0461
1588 Multidrug resistance protein 1 ABCB1 0.0349
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0231
6702 Organic hydroperoxide resistance protein, putative VC_A1006 0.0228
4587 Carbapenem-hydrolyzing beta-lactamase blaB-1 blaB1 0.0228
332 Beta-lactamase blaZ 0.0228
2478 Beta-lactamase ampC 0.0228
2613 Beta-lactamase ampC 0.0228
2635 Beta-lactamase ampC 0.0228
2700 Beta-lactamase penP 0.0228
5445 Beta-lactamase blaB 0.0228
6019 Beta-lactamase SHV-7 0.0228
6701 Beta-lactamase cphA 0.0228
4586 FEZ-1 protein blaFEZ-1 0.0228
3923 Cholinesterase BCHE 0.0227
3917 Methylenetetrahydrofolate reductase MTHFR 0.0182
4604 Liver carboxylesterase 1 CES1 0.0158
5754 Metallo-beta-lactamase L1 Not Available 0.0143
2998 Sialic acid-binding Ig-like lectin 7 SIGLEC7 0.0142
3626 Probable polysaccharide deacetylase pdaA pdaA 0.0138
4787 Envelope glycoprotein gp160 env 0.0125
4820 Envelope glycoprotein gp160 env 0.0125
5727 Envelope glycoprotein gp160 env 0.0125
707 72 kDa type IV collagenase MMP2 0.0119
1373 Glucosylceramidase GBA 0.0114
4666 Fucose-binding lectin PA-IIL lecB 0.0114
1729 Solute carrier family 22 member 6 SLC22A6 0.011
3140 Hemagglutinin-neuraminidase HN 0.0104
3609 Hemagglutinin-neuraminidase HN 0.0104
65 Matrix metalloproteinase-9 Not Available 0.0096
4785 Ig gamma-1 chain C region IGHG1 0.0074
6143 Solute carrier family 22 member 7 SLC22A7 0.0068
474 Acetylcholinesterase ACHE 0.006
6142 Solute carrier family 22 member 8 SLC22A8 0.006
587 Serum albumin ALB 0.0054
4119 Cytochrome P450 2D6 CYP2D6 0.0045
4512 Cytochrome P450 3A4 CYP3A4 0.0041
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