Approval Year
| Substance Class |
Structurally Diverse
Created
by
admin
on
Edited
Fri Dec 15 18:19:47 UTC 2023
by
admin
on
Fri Dec 15 18:19:47 UTC 2023
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| Source Materials Class | ORGANISM |
| Source Materials Type | BACTERIUM |
| Organism Family | Clostridiaceae |
| Organism Genus | Clostridium |
| Organism Species | difficile |
| Author | (HALL AND O'TOOLE, 1935) PREVOT, 1938 |
| Part | WHOLE |
| Record UNII |
PJX89V9R6N
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| Record Status |
Validated (UNII)
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| Record Version |
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1496
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960739
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1534764
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WBM6
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admin on Fri Dec 15 18:19:47 UTC 2023 , Edited by admin on Fri Dec 15 18:19:47 UTC 2023
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Clostridium difficile
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admin on Fri Dec 15 18:19:47 UTC 2023 , Edited by admin on Fri Dec 15 18:19:47 UTC 2023
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PJX89V9R6N
Created by
admin on Fri Dec 15 18:19:47 UTC 2023 , Edited by admin on Fri Dec 15 18:19:47 UTC 2023
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PJX89V9R6N
Created by
admin on Fri Dec 15 18:19:47 UTC 2023 , Edited by admin on Fri Dec 15 18:19:47 UTC 2023
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PRIMARY |
| Related Record | Type | Details | ||
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INHIBITOR->TARGET ORGANISM |
RESULTS: REP3123 was active against a collection of 108 clinical isolates of C. difficile and against epidemic, moxifloxacin-resistant BI/NAP1/027 strains (MIC range=0.5-1 mg/L and MIC(90) = 1 mg/L). The spectrum of activity included clinically important aerobic Gram-positive cocci such as Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis and Enterococcus faecium (MIC(90)s < 1 mg/L), but REP3123 was not active against most Gram-negative bacteria. REP3123 targeted C. difficile MetRS with a calculated inhibition constant (K(i)) of 0.020 nM, and selectivity was >1000-fold over human mitochondrial and cytoplasmic MetRS. The specific mode of action within bacterial cells was demonstrated by macromolecular synthesis assays that showed inhibition of protein synthesis by REP3123, and by metS overexpression, which resulted in a 16-fold increase in MIC for REP3123. Spontaneous REP3123-resistant mutants of C. difficile (MICs, 4-128 mg/L) arose with frequencies of 10(-8)-10(-9) and harboured distinct point mutations within the metS gene, resulting in 13 different amino acid substitutions. Most of the MetRS substitutions caused reduced catalytic efficiency and a growth fitness burden.
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C. difficile ATCC 9689
MIC
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The rate of recurrent C. difficile infection was significantly lower with bezlotoxumab.
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ACTIVE MOIETY |
