Candoxatril
| Candoxatril | |
|---|---|
 | |
| IUPAC name 4-{[(1-{3-(2,3-dihydro-1H-inden-5-yloxy)-2-[(2-methoxyethoxy)methyl]-3-oxopropyl}cyclopentyl)carbonyl]amino}cyclohexanecarboxylic acid | |
| Identifiers | |
| CAS number | 118785-03-8 |
| PubChem | 122116, 5362417 |
| ChemSpider | 16736409 |
| DrugBank | DB00616 |
| MeSH | candoxatril |
| Jmol-3D images | Image 1 |
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| Properties | |
| Molecular formula | C29H41NO7 |
| Molar mass | 515.638 |
| Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa) | |
| Infobox references | |
Candoxatril is the orally active prodrug[1] of candoxatrilat (UK-73967) human neutral endopeptidase (Neprilysin) as the neutral endopeptidase 24.11[2] complexed (RB-101) with phosphoramidon degrades and inactivates[3] a number of bioactive peptides. Two multiply connected folding domains[3] of the neutral endopeptidase locus[3] splicing of exons 1, 2a, or 2b to the common exon 3 composed of 24 exons of the human CALLA/NEP gene[2] containing the active site, it is known as peptidase family M13 (neprilysin family, clan MA(E)) the gluzincins a faint but significant structural relationship of the metzincins[4][5][6][7] to the thermolysin-like enzymes,[5] Zincin is the simplest descriptor of biological space.[8] The structure reveals two multiply connected folding domains which embrace a large central cavity containing the active site of the 5-indanyl ester prodrug candoxatril[9] and differs from phosphoramidon [N-(N-(((6-Deoxy-α-L-mannopyranosyl)oxy)hydroxyphosphinyl)-L- leucyl)-L-tryptophan] in several respects the structure of human neutral endopeptidase complexed with phosphoramidon is lost due to desolvation[9] of the enzyme and ligand on formation of the complex Candoxatril.
See also
References
- ↑ Maw GN, Stobie A, Planken S, Pryde DC, Sanderson V, Platts MY, Corless M, Stacey P, Wayman C, Van Der Graaf P, Kohl C, Coggon S, Beaumont K. (January 2006). "The discovery of small molecule inhibitors of neutral endopeptidase. Structure-activity studies on functionalized glutaramides.". Chem Biol Drug Des. 67 (1): 74–77. doi:10.1111/j.1747-0285.2005.00320.x. PMID 16492151.
- ↑ 2.0 2.1 D'Adamio L, Shipp MA, Masteller EL, Reinherz EL. (September 1989). "Organization of the gene encoding common acute lymphoblastic leukemia antigen (neutral endopeptidase 24.11): multiple miniexons and separate 5' untranslated regions.". Proc Natl Acad Sci U S A. 86 (18): 7103–7107. doi:10.1073/pnas.86.18.7103. PMC 298003. PMID 2528730.
- ↑ 3.0 3.1 3.2 Oefner C , D'Arcy A , Hennig M , Winkler FK , Dale GE (February 2000). "Structure of human neutral endopeptidase (Neprilysin) complexed with phosphoramidon.". J.MOL.BIOL 296 (2): 341–349. doi:10.1006/jmbi.1999.3492. PMID 10669592.
- ↑ Nigel M. Hooper (October 1994). "Families of zinc metalloproteases.". FEBS Lett. 354 (1): 1–6. doi:10.1016/0014-5793(94)01079-X. PMID 7957888.
- ↑ 5.0 5.1 Stöcker W, Grams F, Baumann U, Reinemer P, Gomis-Rüth FX, McKay DB, Bode W. (May 1995). "The metzincins--topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a superfamily of zinc-peptidases.". Protein Sci. 4 (5): 823–840. doi:10.1002/pro.5560040502. PMC 2143131. PMID 7663339.
- ↑ "Neutral zinc metallopeptidases, zinc-binding region signature as a superfamily,known as the metzincins (EC 3.4.15.1). ExPASy: PDOC00129".
- ↑ "EC 3.4.15.1 - Peptidyl-dipeptidase A in contrast to EC 3.4.15.4 atriopeptin. EMBL-EBI: PDOC00129".
- ↑ McArdle BM, Quinn RJ. (April 2007). "Identification of Protein Fold Topology Shared between Different Folds Inhibited by Natural Products". ChemBioChem 8 (7): 788–798. doi:10.1002/cbic.200700035. PMID 17429823.
- ↑ 9.0 9.1 Holland, D.R., Barclay, P.L., Danilewicz, J.C., Matthews, B.W., James, K. (January 1994). "Inhibition of thermolysin and neutral endopeptidase 24.11 by a novel glutaramide derivative: X-ray structure determination of the thermolysin-inhibitor complex.". Biochemistry 33 (1): 51–56. doi:10.1021/bi00167a007. PMID 8286362.