CLAVULANIC ACID

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Synonyms
Status
Molecule Category UNKNOWN
UNII 23521W1S24
EPA CompTox DTXSID2022830

Structure

InChI Key HZZVJAQRINQKSD-PBFISZAISA-N
Smiles O=C(O)[C@H]1/C(=C/CO)O[C@@H]2CC(=O)N21
InChI
InChI=1S/C8H9NO5/c10-2-1-4-7(8(12)13)9-5(11)3-6(9)14-4/h1,6-7,10H,2-3H2,(H,12,13)/b4-1-/t6-,7-/m1/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C8H9NO5
Molecular Weight 199.16
AlogP -1.1
Hydrogen Bond Acceptor 4.0
Hydrogen Bond Donor 2.0
Number of Rotational Bond 2.0
Polar Surface Area 87.07
Molecular species ACID
Aromatic Rings 0.0
Heavy Atoms 14.0
Assay Description Organism Bioactivity Reference
Inhibitory activity against Branhamella catarrhalis 89001 Class-III BRO-1 type beta-lactamase enzyme b.catarr 0.006 ug.mL-1
Inhibitory activity against Bacteroides fragilis 88854 Class-I beta-lactamase enzyme Bacteroides fragilis 0.05 ug.mL-1
Inhibitory activity against Citrobacter freundii 87470 Class-I beta-lactamase enzyme Citrobacter freundii 3.2 ug.mL-1
Inhibitory activity against Enterobacter cloacae HC8 Class-I beta-lactamase enzyme type P99 Enterobacter cloacae 6.3 ug.mL-1
Compound was evaluated for beta-lactamase inhibition activity of Escherichia coli after 15 min of pre-incubation with the enzyme at 37 degree C Escherichia coli 40.0 nM
Concentration required for its inhibitory activity against Escherichia coli JT4(TEM1) class A beta-lactamase Escherichia coli 29.0 ug.mL-1
Concentration required for its inhibitory activity against Escherichia coli K12(OXA1) class D beta-lactamase Escherichia coli 350.0 ug.mL-1
Concentration required for its inhibitory activity against Escherichia coli K12(PSE4) class A beta-lactamase Escherichia coli 15.0 ug.mL-1
Inhibitory activity against beta-Lactamase enzyme derived from Escherichia coli WC3310 TEM-2 Escherichia coli 60.0 nM
Inhibitory activity against Escherichia coli TEM-3 Beta-lactamase Escherichia coli 15.0 nM Inhibitory activity against Escherichia coli TEM-3 Beta-lactamase Escherichia coli 15.0 nM
Inhibitory activity against Escherichia coli HA208 Class-III SHV-1 type beta-lactamase enzyme Escherichia coli 0.004 ug.mL-1
Inhibitory activity against Escherichia coli HA209 Class-V OXA-1 type beta-lactamase enzyme Escherichia coli 0.08 ug.mL-1
Inhibitory activity against Escherichia coli HA58R Class-III TEM-1 type beta-lactamase enzyme Escherichia coli 0.008 ug.mL-1
Inhibition constant (Ki) for TEM-1 beta-lactamase Escherichia coli 800.0 nM
Inhibitory activity against Klebsiella oxytoca HC7 Class-IV K1 type beta-lactamase enzyme Klebsiella oxytoca 0.006 ug.mL-1
Concentration required for its inhibitory activity against Proteus mirabilis C889 class A beta-lactamase Proteus mirabilis 19.0 ug.mL-1
Inhibitory activity against Proteus vulgaris HJ33C Class-I beta-lactamase enzyme Proteus vulgaris 0.013 ug.mL-1
Inhibitory concentration was evaluated as concentration required for 50% inhibition of Pseudomonas aeruginosa 18SH Beta-lactamase Pseudomonas aeruginosa 800.0 nM
Concentration required for its inhibitory activity against Staphylococcus aureus Russel class A beta-lactamase Staphylococcus aureus 30.0 ug.mL-1
Inhibitory activity against Penicillinase from Staphylococcus aureus TH-14 using piperacillin (40 uM) as a substrate Staphylococcus aureus 80.0 nM
Inhibitory activity against Staphylococcus aureus CJ8 beta-lactamase enzyme Staphylococcus aureus 0.005 ug.mL-1
Inhibitory activity at beta-lactamase I from Bacillus cereus expressed as percent inhibition of beta-lactam hydrolysis at a concentration of 1.0 umol/L Bacillus cereus 9.0 %
Inhibitory activity at beta-lactamase I from Bacillus cereus expressed as percent inhibition of beta-lactam hydrolysis at a concentration of 10.0 umol/L Bacillus cereus 33.0 %
Inhibitory activity at beta-lactamase I from Bacillus cereus expressed as percent inhibition of beta-lactam hydrolysis at a concentration of 100.0 umol/L Bacillus cereus 78.0 %
Inhibitory activity against cephalosporinase from Proteus vulgaris TH-147 using cephalexin (40 uM) as a substrate Proteus vulgaris 160.0 nM
Tested in vitro for the beta lactamase inhibition of Escherichia coli TEM Escherichia coli 40.0 nM
Time dependent inhibition of hydrolysis of nitrocefin after 5 min pre-incubation with TEM-1 beta-lactamase (class 1) None 65.0 nM
Inhibition of Escherichia coli BL21(DE3) beta-lactamase TEM151 Escherichia coli 170.0 nM
Inhibition of Escherichia coli BL21(DE3) beta-lactamase TEM28 Escherichia coli 20.0 nM
Inhibition of Escherichia coli BL21(DE3) beta-lactamase TEM36 Escherichia coli 80.0 nM
Inhibition of Escherichia coli BL21(DE3) beta-lactamase TEM1 Escherichia coli 25.0 nM
Inhibition of Citrobacter gillenii CIP 106783 Beta-lactamase GIL1 expressed in Escherichia coli DH10B Citrobacter gillenii 9.0 nM
Inhibition of Escherichia coli TEM1 Escherichia coli 30.0 nM
Inhibition of Escherichia coli SHV1 Escherichia coli 28.0 nM
Inhibition of Acinetobacter johnsonii SCO1 Acinetobacter johnsonii 300.0 nM
Inhibition of Escherichia coli beta-lactamase SCO1 Escherichia coli 70.0 nM
Inhibition of Escherichia coli K12 CARB1 Escherichia coli 100.0 nM
Inhibition of Escherichia coli K12 TEM1 Escherichia coli 170.0 nM
Inhibition of Escherichia coli K-12 beta-lactamase PSE-4 assessed as inhibition of nitrocefin hydrolysis preincubated for 5 mins by microtiter plate assay Escherichia coli K-12 0.015 ug.mL-1
Inhibition of Escherichia coli K-12 beta-lactamase OXA1 assessed as inhibition of nitrocefin hydrolysis pre-incubated for 5 mins by microtiter plate assay Escherichia coli K-12 0.35 ug.mL-1
Inhibition of Escherichia coli JT4 beta-lactamase TEM1 assessed as inhibition of nitrocefin hydrolysis preincubated for 5 mins by microtiter plate assay Escherichia coli 0.029 ug.mL-1
Inhibition of Pseudomonas aeruginosa A beta-lactamase assessed as inhibition of nitrocefin hydrolysis preincubated for 5 mins by microtiter plate assay Pseudomonas aeruginosa 740.0 ug.mL-1
Inhibition of Enterobacter cloacae P99 beta-lactamase assessed as inhibition of nitrocefin hydrolysis pre-incubated for 5 mins by microtiter plate assay Enterobacter cloacae 155.0 ug.mL-1
Inhibition of Proteus mirabilis C889 beta-lactamase assessed as inhibition of nitrocefin hydrolysis preincubated for 5 mins by microtiter plate assay Proteus mirabilis 0.019 ug.mL-1
Inhibition of Staphylococcus aureus Russell beta-lactamase assessed as inhibition of nitrocefin hydrolysis pre-incubated for 5 mins by microtiter plate assay Staphylococcus aureus 0.03 ug.mL-1
Inhibition of Escherichia coli CTX-M-15 Escherichia coli 9.0 nM
Inhibition of Escherichia coli DH5alpha beta-lactamase TEM-12 Escherichia coli 20.0 nM
Inhibition of Escherichia coli DH5alpha beta-lactamase TEM-1 Escherichia coli 80.0 nM
Inhibition of Bacillus clausii NR beta-lactamase BCL1 expressed in Escherichia coli BL21 (DE3) Bacillus clausii 85.0 nM
Inhibition of Pseudomonas luteola LAM Beta-lactamase LUT-1 Pseudomonas luteola 36.0 nM
Inhibition of Pseudomonas aeruginosa 531 beta-lactamase BEL-2 Pseudomonas aeruginosa 100.0 nM
Inhibition of Pseudomonas aeruginosa 51170 beta-lactamase BEL-1 Pseudomonas aeruginosa 100.0 nM
Inhibition of Pseudomonas aeruginosa GES-13 beta lactamase Pseudomonas aeruginosa 100.0 nM
Inhibition of Klebsiella pneumoniae Beta-Lactamase SHV-1 Klebsiella pneumoniae 170.0 nM
Inhibition of Klebsiella pneumoniae Beta-Lactamase SHV-1 Klebsiella pneumoniae 170.0 nM
Inhibition of Klebsiella pneumoniae Beta-Lactamase SHV-55 Klebsiella pneumoniae 20.0 nM
Inhibition of Shigella sonnei UIH-1 beta-lactamase CTX-M-64 by spectrophotometry in presence of 100 uM nitrocefin Shigella sonnei 10.0 nM
Inhibition of Salmonella enterica serotype Westhampton beta-lactamase CTX-M-53 Salmonella enterica subsp. enterica serovar Westhampton 10.0 nM
Inhibition of recombinant beta-lactamase RTG4 expressed in Escherichia coli TOP10 by nitrocefin hydrolysis assay None 70.0 nM
Inhibition of recombinant beta-lactamase RTG3 expressed in Escherichia coli TOP10 by nitrocefin hydrolysis assay None 100.0 nM
Inhibition of Klebsiella pneumoniae Beta-lactamase SHV-1 Klebsiella pneumoniae 28.0 nM
Inhibition of Beta-lactamase TEM-1 None 30.0 nM
Inhibition of beta-lactamase SHV-4 assessed as nitrocefin hydrolysis after 5 mins enzyme-compound preincubation None 4.0 nM
Inhibition of beta-lactamase CTX-M-15 assessed as nitrocefin hydrolysis after 5 mins enzyme-compound preincubation None 12.0 nM
Inhibition of beta-lactamase TEM- 1 assessed as nitrocefin hydrolysis after 5 mins enzyme-compound preincubation None 58.0 nM
Inhibition of beta-lactamase TEM-1 after 5 seconds incubation with nitrocefin substrate by spectrophotometry None 800.0 nM
Inhibition of Beta-lactamase GES-1 E104, G170 mutant preincubated for 5 mins before substrate addition using cephalothin substrate by spectrophotometry None 100.0 nM
Inhibition of Beta-lactamase GES-7 K104, G170 mutant preincubated for 5 mins before substrate addition using cephalothin substrate by spectrophotometry None 800.0 nM
Inhibition of Beta-lactamase GES-2 E104, N170 mutant preincubated for 5 mins before substrate addition using cephalothin substrate by spectrophotometry None 80.0 nM
Inhibition of Beta-lactamase GES-5 E104, S170 mutant preincubated for 5 mins before substrate addition using cephalothin substrate by spectrophotometry None 500.0 nM
Inhibition of Beta-lactamase GES-13 K104, N170 mutant preincubated for 5 mins before substrate addition using cephalothin substrate by spectrophotometry None 90.0 nM
Inhibition of Escherichia coli recombinant CTX-M-15 assessed as substrate nitrocefin degradation preincubated for 10 mins followed by substrate addition measured every 10 secs for 10 mins by spectrophotometric analysis Escherichia coli 27.0 nM
Inhibition of Escherichia coli recombinant SHV-12 assessed as substrate nitrocefin degradation preincubated for 10 mins followed by substrate addition measured every 10 secs for 10 mins by spectrophotometric analysis Escherichia coli 39.0 nM
Inhibition of Escherichia coli recombinant TEM-10 assessed as substrate nitrocefin degradation preincubated for 10 mins followed by substrate addition measured every 10 secs for 10 mins by spectrophotometric analysis Escherichia coli 20.0 nM
Cell Free Inhibition Assay: The inhibitory concentrations (IC50, [uM]) of the beta -lactamase inhibitors against purified TEM-1, SHV-1 and AmpC beta -lactamases are assessed by determining the concentration of inhibitor at which 50% of the nitrocefin hydrolysis is inhibited by the particular enzyme. Assays are performed with beta -lactamases expressed in the pET system (Novagen, San Diego, Calif.) without signal peptides. They contain an N-terminal hexa-Histidine tag that is used for purification on Ni-NTA (Qiagen, Hilden, Germany). The compounds are prepared as 50 mM stocks in DMSO and diluted into buffer P1 (50 mM phosphate, pH 7) to a final concentration of 10% DMSO. All further dilutions are done in P2 (P1 with 10% DMSO). Enzyme and compound dilutions are pre-incubated for 10 min at 37 C. and the reaction is started with the addition of pre-warmed (37 C.) nitrocefin at a final concentration of 50 mM. The change in absorption at 490 nm is followed at 37 C. for 10 min with 30 s intervals. None 30.3 nM
Cell Free Inhibition Assay: The inhibitory concentrations (IC50, [uM]) of the beta -lactamase inhibitors against purified TEM-1, SHV-1 and AmpC beta -lactamases are assessed by determining the concentration of inhibitor at which 50% of the nitrocefin hydrolysis is inhibited by the particular enzyme. Assays are performed with beta -lactamases expressed in the pET system (Novagen, San Diego, Calif.) without signal peptides. They contain an N-terminal hexa-Histidine tag that is used for purification on Ni-NTA (Qiagen, Hilden, Germany). The compounds are prepared as 50 mM stocks in DMSO and diluted into buffer P1 (50 mM phosphate, pH 7) to a final concentration of 10% DMSO. All further dilutions are done in P2 (P1 with 10% DMSO). Enzyme and compound dilutions are pre-incubated for 10 min at 37 C. and the reaction is started with the addition of pre-warmed (37 C.) nitrocefin at a final concentration of 50 mM. The change in absorption at 490 nm is followed at 37 C. for 10 min with 30 s intervals. None 29.5 nM
Inhibition of bacterial SHV-5 using cefotaxime as substrate preincubated for 15 mins followed by susbtrate addition and measured after 10 mins by spectrophotometric method Bacteria 12.0 nM
Inhibition of bacterial CTX-M-15 using cefotaxime as substrate preincubated for 15 mins followed by susbtrate addition and measured after 10 mins by spectrophotometric method Bacteria 40.0 nM
Inhibition of bacterial OXA-1 using nitrocefin as substrate preincubated for 15 mins followed by susbtrate addition and measured after 10 mins by spectrophotometric method Bacteria 120.0 nM

Cross References

Resources Reference
ChEBI 48947
ChEMBL CHEMBL777
DrugBank DB00766
DrugCentral 669
FDA SRS 23521W1S24
Human Metabolome Database HMDB0014904
Guide to Pharmacology 11128
KEGG C06662
PDB J01
PharmGKB PA164742987
PubChem 5280980
SureChEMBL SCHEMBL6093
ZINC ZINC000003830569
CONTENTS