Repositioning Candidate Details
| Candidate ID: | R0115 |
| Source ID: | DB00410 |
| Source Type: | approved; investigational; vet_approved |
| Compound Type: | small molecule |
| Compound Name: | Mupirocin |
| Synonyms: | |
| Molecular Formula: | C26H44O9 |
| SMILES: | C[C@H](O)[C@H](C)[C@@H]1O[C@H]1C[C@H]1CO[C@@H](C\C(C)=C\C(=O)OCCCCCCCCC(O)=O)[C@H](O)[C@@H]1O |
| Structure: |
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| DrugBank Description: | Mupirocin, formerly termed pseudomonic acid A,[A178531] is a novel antibacterial agent with a unique chemical structure and mode of action apart from other antibiotic agents. Produced by fermentation using the organism _Pseudomonas fluorescens_, mupirocin is a naturally-occurring antibiotic that displays a broad-specturm activity against many gram-positive bacteria and certain gram-negative bacteria _in vitro_.[L10580] It primarily works by inhibiting bacterial protein synthesis. Due to its unique mode of action of inhibiting the activity of bacterial isoleucyl-tRNA synthetase, mupirocin does not demonstrate cross-resistance with other classes of antimicrobial agents, giving it a therapeutic advantage.[L10580] It is available in topical formulations only due to extensive systemic metabolism[A178531] and is used in the treatment of impetigo caused by _Staphylococcus aureus_ and _Streptococcus pyogenes_ and traumatic skin lesions due to secondary skin infections caused by _S. aureus_ and _S. pyogenes_. There is also some clinical evidence that suggests the potential role of mupirocin in eradicating nasal carriage of Staphylococci when administered intranasally.[A178531,A178591] Mupirocin is commonly marketed under the brand name Bactroban. |
| CAS Number: | 12650-69-0 |
| Molecular Weight: | 500.6222 |
| DrugBank Indication: | Indicated for the treatment of impetigo and secondary skin infections, leading to traumatic skin lesions, due to _Staphylococcus aureus_ and _Streptococcus pyogenes_.[L10580] |
| DrugBank Pharmacology: | Mupirocin is reported to be active against susceptible aerobic gram-positive cocci, such as _Staphylococcus aureus_, _Staphylococcus epidermidis_, and other beta-hemolytic streptococci_Streptococcus pyogenes_.[A178594] It mediates its antibacterial activity by inhibiting the bacterial protein synthesis and formation of bacterial proteins essential for survival. The minimum bactericidal concentration (MBC) against relevant pathogens is generally eight-fold to thirty-fold higher than the minimum inhibitory concentration (MIC).[L10580] In one clinical study investigating the therapeutic effectiveness of topical mupirocin in impetigo, the therapeutic response rate was about 94 to 98% after one week following the end of therapy.[L10580] In clinical studies of patients with primary and secondary skin infections, both elimination of the bacterial pathogen and clinical cure or improvement hav been demonstrated in over 90% of patients receiving topical mupirocin.[A178591] Mupirocin resistance as high as 81% has been reported previously.[A178600] Resistance to mupirocin, which occurs more frequently in methicillin-resistant than methicillin-susceptible staphylococci, may occur with the production of a modified isoleucyl-tRNA synthetase, or the acquisition of, by genetic transfer, a plasmid mediating a new isoleucyl-tRNA synthetase.[L10580] |
| DrugBank MoA: | Mupirocin specifically and reversibly binds to bacterial isoleucyl transfer-RNA (tRNA) synthetase, which is an enzyme that promotes the conversion of isoleucine and tRNA to isoleucyl-tRNA. Inhibition of this enzyme subsequently leads to the inhibition of the bacterial protein and RNA synthesis.[A178531] Mupirocin is bacteriostatic at lower concentrations but it exerts bactericidal effects with prolonged exposure, killing 90-99% of susceptible bacteria over a 24 hour period.[A178552] |
| Targets: | Isoleucine--tRNA ligase |
| Inclusion Criteria: |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T03 | Angiotensin-converting enzyme | ACE | INHIBITOR | Target is a single protein chain | P12821 | ACE_HUMAN | Details |
| T47 | Sialin | SLC17A5 | Target is a single protein chain | Q9NRA2 | SLC17A5_HUMAN | Details | |
| T15 | Steryl-sulfatase | STS | INHIBITOR | Hydrolase | P08842 | STS_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I02 | 1184 | nephrotic syndrome | "A nephrosis characterized by marked increase in glomerular protein permeability resulting in marked elevation of urine protein levels, hypoalbuminemia, hyperlipidemia, and hypercoagulability." [url:https\://en.wikipedia.org/wiki/Nephrotic_syndrome, url:https\://www.niddk.nih.gov/health-information/kidney-disease/nephrotic-syndrome-adults] | Details |