Repositioning Candidate Details
| Candidate ID: | R1432 |
| Source ID: | DB12107 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Vaborbactam |
| Synonyms: | Vaborbactam |
| Molecular Formula: | C12H16BNO5S |
| SMILES: | OB1O[C@H](CC(O)=O)CC[C@@H]1NC(=O)CC1=CC=CS1 |
| Structure: |
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| DrugBank Description: | Vaborbactam is a β-lactamase inhibitor based on a cyclic boronic acid pharmacophore. It has been used in trials investigating the treatment of bacterial infections in subjects with varying degrees of renal insufficiency. In August 2017, a combination antibacterial therapy under the market name Vabomere was approved by the FDA for the treatment of adult patients with complicated urinary tract infections (cUTI). Vabomere consists of vaborbactam and for intravenous administration. Vaborbactam is added to the therapy to reduce the extent meropenem degradation by inhibiting the serine beta-lactamases expressed by the microorganism of target. The treatment aims to resolve infection-related symptoms of cUTI and achieve negative urine culture, when the infections are proven or strongly suspected to be caused by susceptible bacteria. |
| CAS Number: | 1360457-46-0 |
| Molecular Weight: | 297.13 |
| DrugBank Indication: | Indicated in combination with meropenem for the treatment of patients 18 years of age and older with complicated urinary tract infections (cUTI) including pyelonephritis caused by the following susceptible microorganisms: _Escherichia coli_, _Klebsiella pneumoniae_, and _Enterobacter cloacae_ species complex. |
| DrugBank Pharmacology: | Vaborbactam shows no antibacterial activity alone; it serves to restore the antibacterial activity of other antibacterial agents such as meropenem by attenuating their degradation by inhibiting certain serine beta-lactamases of microorganisms. Vaborbactam does not decrease the activity of meropenem against meropenem-susceptible organisms. Vaborbactam in combination with meropenem, which is a penem antibacterial drug, potentiates the bactericidal actions of meropenem against carbapenem-resistant KPC-containing _Escherichia coli_, _Klebsiella pneumoniae_, and _Enterobacter cloacae_ in a concentration-dependent manner. It restored the antimicrobial activity of meropenem in animal models of infection caused by some meropenem non-susceptible KPC-producing Enterobacteriaceae. |
| DrugBank MoA: | Vaborbactam is a cyclic boronic acid pharmacophore β-lactamase inhibitor that elicits potent inhibition of _Klebsiella pneumoniae_ carbapenemase (KPC) enzymes and other Ambler class A and C enzymes such as serine β-lactamases that confer resistance to commonly-used antibiotics such as Carbapenems. Vaborbactam is a potent inhibitor of class A carbapenemases, such as KPC, as well as an inhibitor of other class A (CTX-M, SHV, TEM) and class C (P99, MIR, FOX) beta-lactamases. Vaborbactam interacts with β-lactamases of Ambler classes A and C via precovalent and covalent binding. It exerts no inhibitory actions on class D or class B carbapenemases. The production of contemporary β-lactamase by bacterial isolates potentiate the degradation of β-lactam antibiotic agents, rendering them clinically ineffective and posing challenges for patients receiving the standard antibiotic therapy. In combination with meropenem, varborbactam acts as a non-suicidal beta-lactamase inhibitor that protects meropenem from degradation mediated by serine beta-lactamases such as _Klebsiella pneumoniae_ carbapenemase (KPC). |
| Targets: | Beta-lactamase inhibitor; Carbapenem-hydrolyzing beta-lactamase KPC inhibitor; Beta-lactamase (KPC-2) inhibitor; Beta-lactamase CTX-M inhibitor; Beta-lactamase (blaSHV) inhibitor; Beta-lactamase SHV-1 inhibitor; Beta-lactamase TEM inhibitor; Beta-lactamase (MIR-1) inhibitor; Beta-lactamase inhibitor |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
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| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
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| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I01 | 552 | Pneumonia | A lung disease that involves lung parenchyma or alveolar inflammation and abnormal alveolar filling with fluid (consolidation and exudation). It results from a variety of causes including infection with bacteria, viruses, fungi or parasites, and chemical or physical injury to the lungs. It is accompanied by fever, chills, cough, and difficulty in breathing. http://en.wikipedia.org/wiki/Pneumonia | disease of anatomical entity/respiratory system disease/ lower respiratory tract disease/lung disease | Details |
| I09 | 104 | Bacterial infectious disease | A disease by infectious agent that results_in infection, has_material_basis_in Bacteria. http://en.wikipedia.org/wiki/Pathogenic_bacteria | disease by infectious agent | Details |