Repositioning Candidate Details
| Candidate ID: | R1532 |
| Source ID: | DB14569 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Tedizolid |
| Synonyms: | Tedizolid; Torezolid |
| Molecular Formula: | C17H15FN6O3 |
| SMILES: | CN1N=NC(=N1)C1=NC=C(C=C1)C1=C(F)C=C(C=C1)N1C[C@H](CO)OC1=O |
| Structure: |
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| DrugBank Description: | Drug-resistant bacteria, such as methicillin-resistant _Staphylococcus aureus_, vancomycin-resistant _Enterococcus faecium_, and penicillin-resistant _Streptococcus penumoniae_, represent a massive public health threat. Tedizolid is a member of the oxazolidinone class of antibiotics, which includes the previously approved and is generally effective against multidrug-resistant Gram-positive bacteria. Tedizolid is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and is generally more effective and more tolerable than . Tedizolid was approved by the FDA on June 20, 2014, for sale by Cubist Pharmaceuticals as tedizolid phosphate (SIVEXTRO®). This product is currently available as both an oral tablet and as a powder for intravenous injection. |
| CAS Number: | 856866-72-3 |
| Molecular Weight: | 370.344 |
| DrugBank Indication: | Tedizolid is indicated for the treatment of acute bacterial infections of the skin and skin structure (ABSSSI). To prevent drug resistance, tedizolid should only be used for infections that are caused by susceptible bacteria. |
| DrugBank Pharmacology: | Tedizolid is an oxazolidinone antibiotic that works by inhibiting protein synthesis by bacterial ribosomes. However, oxazolidinone antibiotics can also bind to human mitochondrial, but not cytoplasmic, ribosomes. Mitochondrial protein synthesis inhibition is associated with adverse patient effects such as neurological, hematological, and gastrointestinal toxicity, although tedizolid is tolerated better than the related . Alternative therapies should be considered when treating neutropenic patients with ABSSSI. _Clostridium difficile_-associated diarrhea has been reported in patients treated with tedizolid. |
| DrugBank MoA: | Despite renewed efforts to combat the spread of antimicrobial resistance, multidrug-resistant organisms, including gram-positive bacteria such as methicillin-resistant _Staphylococcus aureus_, remain a threat. Oxazolidinones represent a relatively new class of antibacterials inhibiting protein synthesis that is generally capable of overcoming resistance to other bacterial protein synthesis inhibitors. Protein synthesis involves the action of ribosomes, multi-subunit complexes composed of both protein and ribosomal RNA (rRNA) substituents. Translocation along the length of a messenger RNA and concomitant protein synthesis involves the action of the A, P, and E sites of the peptidyltransferase centre (PTC), which accepts charged aminoacyl-tRNAs and catalyzes the formation of peptide bonds between them. The bacterial 70S ribosome comprises a small (30S) and a large (50S) subunit. Early studies into the mechanism of action of oxazolidinone antibiotics suggested that they inhibit a step in the initiation of protein synthesis. However, this mechanism was inconsistent with mapped resistance mutations, and later studies involving cross-linking and direct structural determination of the binding site revealed that oxazolidinones, including both and tedizolid, bind in the A site of the PTC by interacting with the 23S rRNA component. The structural studies also revealed that oxazolidinone binding alters the conformation of a conserved nucleotide in the 23S rRNA (U2585 in _Escherichia coli_), which renders the PTC non-productive for peptide bond formation. Hence, tedizolid exerts its effect through inhibiting bacterial protein synthesis. |
| Targets: | 23S ribosomal RNA inhibitor |
| Inclusion Criteria: | Indication associated |
