UK-69, 578, a novel inhibitor of EC 3.4.24.11 which increases endogenous ANF levels and is natriuretic and diuretic
A search for potent inhibitors of EC 3.4.24.11, an enzyme which is found most abundantly in the kidney and which degrades atrial natriuretic factor, has led to the identification of UK-69, 578. Structure-activity studies starting from substituted N-carboxymethyl dipeptide inhibitors resulted in the...
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| Veröffentlicht in: | Biochemical and biophysical research communications 1989-10, Vol.164 (1), p.58-65 |
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| creator | Danilewicz, J.C. Barclay, P.L. Barnish, I.T. Brown, D. Campbell, S.F. James, K. Samuels, G.M.R. Terrett, N.K. Wythes, M.J. |
| description | A search for potent inhibitors of EC 3.4.24.11, an enzyme which is found most abundantly in the kidney and which degrades atrial natriuretic factor, has led to the identification of UK-69, 578. Structure-activity studies starting from substituted N-carboxymethyl dipeptide inhibitors resulted in the introduction of a cyclo-alkane P
1′ residue and in the replacement of the aza-link between P
1 and P
1′ residues by a methylene group, with a net ten-fold potency gain. UK-69, 578 increases endogenous ANF levels and produces natriuretic and diuretic responses intravenously in mice. |
| doi_str_mv | 10.1016/0006-291X(89)91682-3 |
| format | Article |
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1′ residue and in the replacement of the aza-link between P
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1′ residue and in the replacement of the aza-link between P
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Psychology</topic><topic>Humans</topic><topic>Hydrolases</topic><topic>kidney</topic><topic>Male</topic><topic>Mice</topic><topic>Microvilli - enzymology</topic><topic>Natriuresis - drug effects</topic><topic>Neprilysin - antagonists & inhibitors</topic><topic>Neprilysin - pharmacology</topic><topic>Rats</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Danilewicz, J.C.</creatorcontrib><creatorcontrib>Barclay, P.L.</creatorcontrib><creatorcontrib>Barnish, I.T.</creatorcontrib><creatorcontrib>Brown, D.</creatorcontrib><creatorcontrib>Campbell, S.F.</creatorcontrib><creatorcontrib>James, K.</creatorcontrib><creatorcontrib>Samuels, G.M.R.</creatorcontrib><creatorcontrib>Terrett, N.K.</creatorcontrib><creatorcontrib>Wythes, M.J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 3</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Danilewicz, J.C.</au><au>Barclay, P.L.</au><au>Barnish, I.T.</au><au>Brown, D.</au><au>Campbell, S.F.</au><au>James, K.</au><au>Samuels, G.M.R.</au><au>Terrett, N.K.</au><au>Wythes, M.J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>UK-69, 578, a novel inhibitor of EC 3.4.24.11 which increases endogenous ANF levels and is natriuretic and diuretic</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>1989-10-16</date><risdate>1989</risdate><volume>164</volume><issue>1</issue><spage>58</spage><epage>65</epage><pages>58-65</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><coden>BBRCA9</coden><abstract>A search for potent inhibitors of EC 3.4.24.11, an enzyme which is found most abundantly in the kidney and which degrades atrial natriuretic factor, has led to the identification of UK-69, 578. Structure-activity studies starting from substituted N-carboxymethyl dipeptide inhibitors resulted in the introduction of a cyclo-alkane P
1′ residue and in the replacement of the aza-link between P
1 and P
1′ residues by a methylene group, with a net ten-fold potency gain. UK-69, 578 increases endogenous ANF levels and produces natriuretic and diuretic responses intravenously in mice.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>2529858</pmid><doi>10.1016/0006-291X(89)91682-3</doi><tpages>8</tpages></addata></record> |
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| ispartof | Biochemical and biophysical research communications, 1989-10, Vol.164 (1), p.58-65 |
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| subjects | Analytical, structural and metabolic biochemistry Animals Atrial Natriuretic Factor - blood Atrial Natriuretic Factor - metabolism Biological and medical sciences Chemical Phenomena Chemistry Cyclohexanecarboxylic Acids Diuretics Enzymes and enzyme inhibitors Fundamental and applied biological sciences. Psychology Humans Hydrolases kidney Male Mice Microvilli - enzymology Natriuresis - drug effects Neprilysin - antagonists & inhibitors Neprilysin - pharmacology Rats |
| title | UK-69, 578, a novel inhibitor of EC 3.4.24.11 which increases endogenous ANF levels and is natriuretic and diuretic |
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