Solithromycin
Solithromycin (CEM-101) is a new, potent and broad-spectrum fluoroketolide antibiotic [1][2].
Antibiotic is an antimicrobial used in the treatment and prevention of bacterial infection.
Solithromycin (CEM-101) is a broad-spectrum fluoroketolide antibiotic. CEM-101 exhibited high potency against diverse groups of Gram-positive and Gram-negative bacteria, including mycoplasma and ureaplasma, as well as bacteria associated with respiratory tract infections and skin infections, with MIC50 values of 0.015 μg/mL and 4 μg/mL, respectively [1]. Solithromycin (CEM-101) bound to the large 50S subunit of the ribosome and inhibited protein biosynthesis. In Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae, solithromycin inhibited cell viability, protein synthesis, and growth rate with IC50 values of 7.5, 40, and 125 ng/ml. Solithromycin also inhibition the formation of the 50S subunit [3]. In monocytic U937 cells, solithromycin inhibited TNFα/CXCL8 production and MMP9 activity. In PBMC isolated from chronic obstructive pulmonary disease (COPD) patients, solithromycin (10 μM) inhibited TNFα release and MMP9 activity. In monocytic U937 cells, solithromycin (10 μM) significantly inhibited NF-κB activity activated by oxidative stress [4].
In C57BL/6J mice, solithromycin also inhibited cigarette smoke-induced neutrophilia and pro-MMP9 production [4]. CEM-101 was also an effective antimicrobial for the prevention and treatment of intrauterine infection [2].
References:
[1]. Putnam SD, Castanheira M, Moet GJ, et al. CEM-101, a novel fluoroketolide: antimicrobial activity against a diverse collection of Gram-positive and Gram-negative bacteria. Diagn Microbiol Infect Dis, 2010, 66(4): 393-401.
[2]. Keelan JA, Kemp MW, Payne MS, et al. Maternal administration of solithromycin, a new, potent, broad-spectrum fluoroketolide antibiotic, achieves fetal and intra-amniotic antimicrobial protection in a pregnant sheep model. Antimicrob Agents Chemother, 2014, 58(1): 447-454.
[3]. Rodgers W, Frazier AD, Champney WS. Solithromycin inhibition of protein synthesis and ribosome biogenesis in Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. Antimicrob Agents Chemother, 2013, 57(4): 1632-1637.
[4]. Kobayashi Y, Wada H, Rossios C, et al. A novel macrolide solithromycin exerts superior anti-inflammatory effect via NF-κB inhibition. J Pharmacol Exp Ther, 2013, 345(1): 76-84.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 845.01 |
| Cas No. | 760981-83-7 |
| Formula | C43H65FN6O10 |
| Solubility | ≥34.35 mg/mL in DMSO |
| Chemical Name | (3aS,4R,7S,9S,10R,11S,13R,15R,15aR)-1-(4-(4-(3-aminophenyl)-1H-1,2,3-triazol-1-yl)butyl)-10-(((2R,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-4-ethyl-7-fluoro-11-methoxy-3a,7,9,11,13,15-hexamethyloctahydro-1H-[1]oxacyclotet |
| SDF | Download SDF |
| Canonical SMILES | CC[C@](O1)([H])[C@@]2([C@@](N(C(O2)=O)CCCCN3C=C(N=N3)C4=CC(N)=CC=C4)([H])[C@@](C([C@](C[C@@]([C@@](O[C@]5([H])[C@@](O)([H])[C@](N(C)C)([H])C[C@@](O5)([H])C)([H])[C@](C([C@@](C1=O)(F)C)=O)([H])C)(OC)C)([H])C)=O)([H])C)C |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
Listeria monocytogenes, Neisseria gonorrhoeae |
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Preparation method |
The solubility of this compound in DMSO is ≥34.35 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.015 microg/mL, 4 microg/mL |
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Applications |
Compared with telithromycin (MIC (50), 0.06 microg/mL), clarithromycin (MIC (50), 0.12 microg/mL) and erythromycin (MIC (50), 0.25 microg/mL), CEM- 101 (MIC (50), 0.015 microg/mL) has high activity against all Gram-positive bacteria. Among Gram-negative bacteria, CEM-101 (MIC (50), 4 microg/mL) also showed high potency against most strains, but compared to other antimicrobials tested in the MIC (50) range For example, from 0.12 microg/mL of levofloxacin to 8 microg/mL of telithromycin, it has the same potency or lower activity. |
| Animal experiment [1]: | |
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Animal models |
Chronically catheterized pregnant ewes |
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Dosage form |
a single maternal intravenous (i.v.) infusion of CEM-101 (10 mg/kg of body weight), a single intra-amniotic (i.a.) injection (1.4 mg/kg of estimated fetal weight) |
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Application |
Maternal plasma (MP), fetal plasma (FP), and amniotic fluid (AF) samples were taken via catheter at intervals of 0 to 72 h postadministration, and concentrations of solithromycin and its bioactive polar metabolites (N-acetyl [NAc]-CEM-101 and CEM-214) were determined. Following maternal i.v. infusion, peak CEM-101 concentrations in MP, FP, and AF were 1,073, 353, and 214 ng/ml, respectively, representing a maternal-to-fetal plasma transfer efficiency of 34%. A single maternal dose resulted in effective concentrations (>30 ng/ml) in MP, FP, and AF sustained for >12 h. NAc-CEM-101 and CEM-214 exhibited delayed accumulation and clearance in FP and AF, resulting in an additive antimicrobial effect (>48 h). Intra-amniotic solithromycin injection resulted in elevated (∼50 μg/ml) and sustained CEM-101 concentrations in AF and significant levels in FP, although the efficiency of amniotic-to-fetal transfer was low (∼1.5%). Our findings suggest that CEM-101 may provide, for the first time, an effective antimicrobial approach for the prevention and treatment of intrauterine infection and early prevention of preterm birth. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Putnam SD, Castanheira M, Moet GJ, Farrell DJ, Jones RN. CEM-101, a novel fluoroketolide: antimicrobial activity against a diverse collection of Gram-positive and Gram-negative bacteria. Diagn Microbiol Infect Dis. 2010 Apr;66(4):393-401. doi: 10.1016/j.diagmicrobio.2009.10.013. PubMed PMID:20022192. [2]. Keelan JA, Kemp MW, Payne MS, Johnson D, Stock SJ, Saito M, Fernandes P, Newnham JP. Maternal administration of solithromycin, a new, potent, broad-spectrum fluoroketolide antibiotic, achieves fetal and intra-amniotic antimicrobial protection in a pregnant sheep model. Antimicrob Agents Chemother. 2014;58(1):447-54. doi: 10.1128/AAC.01743-13. Epub 2013 Nov 4. PubMed PMID:24189250; PubMed Central PMCID: PMC3910757. |
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Quality Control & MSDS
- View current batch:
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Purity = 98.00%
- COA (Certificate Of Analysis)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
