Solithromycin

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Solithromycin
Solithromycin.svg
Systematic (IUPAC) name
(3aS,4R,7S,9R,10R,11R,13R,15R,15aR)-1-[4-[4-(3-aminophenyl)-1H-1,2,3-triazol-1-yl]butyl]-4-ethyl-7-fluorooctahydro-11-methoxy-3a,7,9,11,13,15-hexamethyl-10-{[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy}-2H-Oxacyclotetradecino[4,3-d]oxazole-2,6,8,14(1H,7H,9H)-tetrone
Clinical data
Legal status Phase III clinical trials, North America, South America, Europe, Asia, S. Africa
Routes oral, intravenous
Identifiers
CAS number 760981-83-7 YesY
ATC code None
UNII 9U1ETH79CK N
ChEMBL CHEMBL1240704 N
Synonyms CEM-101; OP-1068
Chemical data
Formula C43H65FN6O10 
Mol. mass 845.01 g/mol
 N (what is this?)  (verify)

Solithromycin (formerly known as CEM-101 and OP-1068) is a novel ketolide antibiotic undergoing clinical development for the treatment of community-acquired pneumonia (CAP)[1] and other infections.[2] It is expected to be the first macrolide antibiotic available in intravenous, oral, and pediatric suspension formulations in over 20 years.

Solithromycin exhibits excellent in vitro activity against a broad spectrum of Gram-positive respiratory tract pathogens,[3][4] including macrolide-resistant strains.[5] Solithromycin has activity against a wide variety of pathogens,[6][7] and further research is being conducted for other infections.

  • September 2011 : Encouraging results from the phase 2 clinical trial versus levofloxacin were reported.[9]

Structure[edit]

X-ray crystallography studies have shown solithromycin, the first fluoroketolide in clinical development, has a third region of interactions with the bacterial ribosome,[10] as compared with two binding sites for other ketolides.

The only currently marketed ketolide, telithromycin, suffers from rare, but serious side effects. Recent studies[11] have shown this to be likely due to the presence of the pyridine-imidazole group of the telithromycin side chain acting as an antagonist towards various nicotinic acetylcholine receptors. Since solithromycin, like azithromycin and clarithromycin, lacks this chemical moiety, it is not expected to cause the adverse events seen with Ketek (telithromycin).

References[edit]

  1. ^ Reinert RR (June 2004). "Clinical efficacy of ketolides in the treatment of respiratory tract infections". The Journal of Antimicrobial Chemotherapy 53 (6): 918–27. doi:10.1093/jac/dkh169. PMID 15117934. 
  2. ^ http://www.cempra.com/research/antibacterials/
  3. ^ Woolsey LN, Castaneira M, Jones RN. (May 2010). "CEM-101 activity against Gram-positive organisms". Antimicrobial Agents and Chemotherapy 54 (5): 2182–2187. doi:10.1128/AAC.01662-09. PMID 2017690. 
  4. ^ Farrell DJ, Sader HS, Castanheira M, Biedenbach DJ, Rhomberg PR, Jones RN. (June 2010). "Antimicrobial characterization of CEM-101 activity against respiratory tract pathogens including multidrug-resistant pneumococcal serogroup 19A isolates". International Journal of Antimicrobial Agents 35 (6): 537–543. doi:10.1016/j.ijantimicag.2010.01.026. PMID 20211548. 
  5. ^ McGhee P, Clark C, Kosowska-Shick K, Nagai K, Dewasse B, Beachel L, Appelbaum PC. (January 2010). "In Vitro Activity of Solithromycin against Streptococcus pneumoniae and Streptococcus pyogenes with Defined Macrolide Resistance Mechanisms". Antimicrobial Agents and Chemotherapy 54 (1): 230–238. doi:10.1128/AAC.01123-09. PMC 2798494. PMID 19884376. Retrieved 2011-02-28. 
  6. ^ Putnam, Shannon D.; Castanheira, Mariana; Moet, Gary J.; Farrell, David J.; Jones, Ronald N. (2010). "CEM-101, a novel fluoroketolide: antimicrobial activity against a diverse collection of Gram-positive and Gram-negative bacteria". Diagnostic Microbiology and Infectious Disease 66 (4): 393–401. doi:10.1016/j.diagmicrobio.2009.10.013. PMID 20022192. 
  7. ^ Putnam, Shannon D.; Sader, Helio S.; Farrell, David J.; Biedenbach, Douglas J.; Castanheira, Mariana (2011). "Antimicrobial characterisation of solithromycin (CEM-101), a novel fluoroketolide: activity against staphylococci and enterococci". International Journal of Antimicrobial Agents 37 (1): 39–45. doi:10.1016/j.ijantimicag.2010.08.021. PMID 21075602. 
  8. ^ "Intravenous (IV) Administration of Cempra Pharmaceutical's Solithromycin (CEM-101) Demonstrates Excellent Systemic Tolerability in a Phase 1 Clinical Trial". 7 May 2011. 
  9. ^ "Cempra antibiotic compound as effective, safer than levofloxacin". 15 Sep 2011. 
  10. ^ Llano-Sotelo B, Dunkle J, Klepacki D, Zhang W, Fernandes P, Cate JH, Mankin AS. (2010). "Binding and Action of CEM-101, a New Fluoroketolide Antibiotic That Inhibits Protein Synthesis". Antimicrobial Agents and Chemotherapy 54 (12): 4961–4970. doi:10.1128/AAC.00860-10. PMC 2981243. PMID 20855725. 
  11. ^ Bertrand D, Bertrand S, Neveu E, Fernandes P. (2010). "Molecular characterization of off-target activities of telithromycin: a potential role for nicotinic acetylcholine receptors". Antimicrobial Agents and Chemotherapy 54 (12): 599–5402. doi:10.1128/AAC.00840-10. PMC 2981250. PMID 20855733. 

Further reading[edit]