Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A range of penicillins have been examined as competitive reversible inhibitors of enkephalinase (neutral endopeptidase; EC 3.4.24.11). Carfecillin (Ki = 0.18 microM) was the most potent inhibitor in the series, whereas cloxacillin (27.5 microM), ampicillin (41.0 microM), nafcillin (58.7 microM) and carbenicillin (158 microM) had moderate potency and benzyl penicillin (885 microM), mezlocillin (473 microM) and azlocillin (556 microM) were weak inhibitors. Structure-activity relationships within the series have been rationalised from a consideration of molecular graphics analysis of the match between receptor binding groups with thiorphan as well as log P values.
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PMID:Novel inhibitors of enkephalin-degrading enzymes. IV: Structure-activity relationships within the penicillins as enkephalinase inhibitors. 128 33

Several penicillins have been found to have pro-antinociceptive properties and also to be enkephalinase (neutral endopeptidase-24.11) inhibitors, carfecillin being the most potent. Carfecillin i.c.v. (but not i.p.) had significant antinociceptive activity in the mouse tail immersion test and completely suppressed abdominal constrictions (acetic acid) in mice (IC50 = 23 micrograms/animal). In combination with (D-Ala2-D-leu5)-enkephalin (DADL) i.c.v. in the abdominal constriction test the complete protection observed was reversed by the opioid receptor antagonist naltrexone. Carfecillin was a competitive inhibitor of enkephalinase from mouse brain striata (IC50 = 207 + 57 nM, cf thiorphan 10.6 +/- 1.9 nM) but did not inhibit other known enkephalin- degrading enzymes. Carfecillin provides a new lead structure for the development of more potent enkephalinase inhibitors.
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PMID:Novel inhibitors of enkephalin-degrading enzymes. I: Inhibitors of enkephalinase by penicillins. 248 37