Repositioning Candidate Details
| Candidate ID: | R0549 |
| Source ID: | DB01627 |
| Source Type: | approved; vet_approved |
| Compound Type: | small molecule |
| Compound Name: | Lincomycin |
| Synonyms: | Cillimycin; LCM; Lincomycin; Lincomycinum |
| Molecular Formula: | C18H34N2O6S |
| SMILES: | [H][C@]1(C[C@@H](CCC)CN1C)C(=O)N[C@H]([C@@H](C)O)[C@H]1O[C@H](SC)[C@H](O)[C@@H](O)[C@H]1O |
| Structure: |
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| DrugBank Description: | Lincomycin is a lincosamide antibiotic first isolated from the soil bacterium _Streptomyces lincolnensis_ in Lincoln, Nebraska. Clinical use of lincomycin has largely been superseded by its semisynthetic derivative due to its higher efficacy and a wider range of susceptible organisms, though lincomycin remains in use. Lincomycin was approved by the FDA on December 29, 1964. |
| CAS Number: | 154-21-2 |
| Molecular Weight: | 406.54 |
| DrugBank Indication: | Lincomycin is indicated for the treatment of serious bacterial infections by susceptible strains of streptococci, pneumococci, and staphylococci in patients who are allergic to penicillins or for situations in which a penicillin is deemed inappropriate. As with all antibacterial agents, lincomycin should only be used to treat infections proven or strongly suspected to be caused by susceptible bacteria. |
| DrugBank Pharmacology: | Lincomycin is a lincosamide antibiotic derived as a natural fermentation product from _Streptomyces lincolnensis_. Like , lincomycin is active against Gram-positive cocci and bacilli as well as Gram-negative cocci and some other organisms such as _Haemophilus_ spp. It is also effective against anaerobic bacteria, though in this regard is generally more potent. Prescribing information highlights that the range of clinically confirmed effectiveness is largely limited to _Staphylococcus_ spp. and _Streptococcus_ spp., with additional activity noted _in vitro_. Lincomycin should be used with caution due to its association with severe cutaneous hypersensitivity reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and acute generalized exanthematous pustulosis, and its potential to precipitate _Clostridium difficile_ associated diarrhea (CDAD), which may lead to fatal colitis. Special care should therefore be exercised when used in elderly patients, individuals with a history of gastrointestinal disease, and those with a history of asthma or significant allergies. Lincomycin for injection may contain benzyl alcohol as a preservative, which has been associated with gasping syndrome in pediatric patients. The serum half-life is extended in patients with hepatic/renal impairment and may require dose adjustments and additional monitoring. Like all antibiotics, lincomycin use may cause overgrowth of non-susceptible organisms, which should be considered. |
| DrugBank MoA: | Lincomycin contains the unusual amino acid moiety propyl hygric acid linked to the sugar moiety α-methylthiolincosamine (α-MTL) that, like other lincosamides, functions as a structural analogue of the 3' end of L-Pro-Met-tRNA and deacylated-tRNA to interact with the 23S rRNA of the 50S bacterial ribosomal subunit. Detailed investigations into the mechanism of the related lincosamide suggested a two-phase binding, instantaneously to the A-site with a shift in equilibrium towards the P-site over several seconds. This shift appears to be due to rotation of the propyl hygric acid moiety, while the α-MTL remains relatively stationary. Recent crystal structures of lincomycin in complex with the 50S ribosomal subunit of _Staphylococcus aureus_ show that the α-MTL moiety forms hydrogen bonds with C2611, A2058, G2505, A2059, and G2503 of the 23S rRNA while the propyl hygric acid moiety interacts only through van der Waals contacts, suggesting it may be free to rotate similar to . This mechanism is supported by the observation that the most common resistance mechanism, which also affects macrolides and streptogramin B (MSLB resistance) involves methylation of A2058; other resistance mechanisms similarly target residues such as A2058, A2059, and C2611. |
| Targets: | 23S ribosomal RNA binder |
| Inclusion Criteria: | Indication associated |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
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