Synonym
REP8839; REP-8839; REP 8839; Bederocin
IUPAC/Chemical Name
2-((3-(((4-bromo-5-(1-fluorovinyl)-3-methylthiophen-2-yl)methyl)amino)propyl)amino)quinolin-4(1H)-one
InChi Key
BGJMKHPWCFXMOW-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H21BrFN3OS/c1-12-17(27-20(13(2)22)19(12)21)11-23-8-5-9-24-18-10-16(26)14-6-3-4-7-15(14)25-18/h3-4,6-7,10,23H,2,5,8-9,11H2,1H3,(H2,24,25,26)
SMILES Code
O=C1C=C(NCCCNCC2=C(C)C(Br)=C(C(F)=C)S2)NC3=C1C=CC=C3
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
The biochemical activity of REP8839 was shown by specific inhibition of purified S. aureus MetS (50% inhibitory concentration, <1.9 nM). Target specificity was confirmed by overexpression of the metS gene in S. aureus, resulting in an eightfold increase in the MIC for REP8839. Macromolecular synthesis assays in the presence of REP8839 demonstrated a dose-dependent inhibition of protein synthesis and RNA synthesis in S. pneumoniae R6, but only protein synthesis was affected in an isogenic rel mutant deficient in the stringent response. Strains with reduced susceptibility to REP8839 were generated by selection of strains with spontaneous mutations and through serial passages. Point mutations within the metS gene were mapped, leading to a total of 23 different amino acid substitutions within MetS that were located around the modeled active site. The most frequent MetS mutations were I57N, leading to a shift in the MIC from 0.06 microg/ml to 4 microg/ml, and G54S, resulting in a MIC of 32 microg/ml that was associated with a reduced growth rate. The mutation prevention concentration was 32 microg/ml in four S. aureus strains (methicillin-sensitive S. aureus and MRSA), which is well below the drug concentration of 2% (20,000 microg/ml) in a topical formulation. In conclusion, we demonstrate by biochemical, physiologic, and genetic mode-of-action studies that REP8839 exerts its antibacterial activity through specific inhibition of MetS, a novel target.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
450.37
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
1: Hussain T, Yogavel M, Sharma A. Inhibition of protein synthesis and malaria parasite development by drug targeting of methionyl-tRNA synthetases. Antimicrob Agents Chemother. 2015 Apr;59(4):1856-67. doi: 10.1128/AAC.02220-13. Epub 2015 Jan 12. PubMed PMID: 25583729; PubMed Central PMCID: PMC4356764.
2: Faqi AS, Bell SJ, Gill S, Colagiovanni DB. An intranasal irritation assessment of antibacterial ointment alone or in combination with mupirocin versus Bactroban Nasal in rabbits. Regul Toxicol Pharmacol. 2009 Oct;55(1):28-32. doi: 10.1016/j.yrtph.2009.05.017. Epub 2009 Jun 2. PubMed PMID: 19497343.
3: Green LS, Bullard JM, Ribble W, Dean F, Ayers DF, Ochsner UA, Janjic N, Jarvis TC. Inhibition of methionyl-tRNA synthetase by REP8839 and effects of resistance mutations on enzyme activity. Antimicrob Agents Chemother. 2009 Jan;53(1):86-94. doi: 10.1128/AAC.00275-08. Epub 2008 Nov 17. PubMed PMID: 19015366; PubMed Central PMCID: PMC2612134.
4: Critchley IA, Ochsner UA. Recent advances in the preclinical evaluation of the topical antibacterial agent REP8839. Curr Opin Chem Biol. 2008 Aug;12(4):409-17. doi: 10.1016/j.cbpa.2008.06.011. Epub 2008 Jul 11. Review. PubMed PMID: 18620074.
5: Ochsner UA, Young CL, Stone KC, Dean FB, Janjic N, Critchley IA. Mode of action and biochemical characterization of REP8839, a novel inhibitor of methionyl-tRNA synthetase. Antimicrob Agents Chemother. 2005 Oct;49(10):4253-62. PubMed PMID: 16189106; PubMed Central PMCID: PMC1251548.
6: Critchley IA, Young CL, Stone KC, Ochsner UA, Guiles J, Tarasow T, Janjic N. Antibacterial activity of REP8839, a new antibiotic for topical use. Antimicrob Agents Chemother. 2005 Oct;49(10):4247-52. PubMed PMID: 16189105; PubMed Central PMCID: PMC1251549.
