Zidebactam (WCK-5107; WCK5107) is a potent β-lactamase inhibitor and also a penicillin-binding protein2 (PBP2) inhibitor with an IC50 of 0.26 μg/mL. It is one of the components ot WCK 5222 (Cefepime-Zidebactam) which is a bicyclo-acyl hydrazide β-lactam enhancer antibiotic with a dual action involving binding to Gram-negative bacterial PBP2 and β-lactamase inhibition. Cefepime/zidebactam demonstrated excellent activity against Enterobacteriaceae and P. aeruginosa, although activity was reduced in carbapenem-non-susceptible isolates. The activity against A. baumannii was reduced and studies examining the therapeutic efficacy in strains with high cefepime/zidebactam MICs are warranted.
Physicochemical Properties
| Molecular Formula | C13H21N5O7S |
| Molecular Weight | 391.4 |
| Exact Mass | 391.116 |
| Elemental Analysis | C, 39.89; H, 5.41; N, 17.89; O, 28.61; S, 8.19 |
| CAS # | 1436861-97-0 |
| Related CAS # | Zidebactam sodium salt;1706777-46-9 |
| PubChem CID | 77846445 |
| Appearance | White to off-white solid powder. |
| Density | 1.6±0.1 g/cm3 |
| Index of Refraction | 1.653 |
| LogP | -3.01 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 26 |
| Complexity | 694 |
| Defined Atom Stereocenter Count | 3 |
| SMILES | [N@]12C[C@H](N(OS(=O)(O)=O)C1=O)CC[C@H]2C(NNC([C@@H]1CCCNC1)=O)=O |
| InChi Key | YCZPXRQPDCXTIO-BBBLOLIVSA-N |
| InChi Code | InChI=1S/C13H21N5O7S/c19-11(8-2-1-5-14-6-8)15-16-12(20)10-4-3-9-7-17(10)13(21)18(9)25-26(22,23)24/h8-10,14H,1-7H2,(H,15,19)(H,16,20)(H,22,23,24)/t8-,9-,10+/m1/s1 |
| Chemical Name | (1R,2S,5R)-7-oxo-2-(2-((R)-piperidine-3-carbonyl)hydrazine-1-carbonyl)-1,6-diazabicyclo[3.2.1]octan-6-yl hydrogen sulfate |
| Synonyms | WCK-5107; WCK 5107; WCK5107; Zidebactam |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | Zidebactam (WCK-5107) has a MIC50 of 0.25 mg/L and inhibits WT Enterobacteriaceae. When tested against E. coli (MIC50/90 0.12/0.12 mg/L) and Enterobacter spp. (MIC50/90 0.12/0.25 mg/L), zebebactam alone exhibited varied efficacy [1]. |
| References |
[1]. WCK 5222 (cefepime/zidebactam) antimicrobial activity tested against Gram-negative organisms producing clinically relevant β-lactamases. J Antimicrob Chemother. 2017 Jun 1;72(6):1696-1703. [2]. WCK 5107 (Zidebactam) and WCK 5153 Are Novel Inhibitors of PBP2 Showing Potent "β-Lactam Enhancer" Activity against Pseudomonas aeruginosa, Including Multidrug-Resistant Metallo-β-Lactamase-Producing High-Risk Clones. Antimicrob Agents Chemother. 2017 May 24;61(6). |
| Additional Infomation | Zidebactam is under investigation in clinical trial NCT02674347 (MAD Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Intravenous Zidebactam in Healthy Adults). |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~638.73 mM) H2O : ~100 mg/mL (~255.49 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.31 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.31 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 3: ≥ 1.98 mg/mL (5.06 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 19.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 4: 100 mg/mL (255.49 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5549 mL | 12.7747 mL | 25.5493 mL | |
| 5 mM | 0.5110 mL | 2.5549 mL | 5.1099 mL | |
| 10 mM | 0.2555 mL | 1.2775 mL | 2.5549 mL |