Specification
Description
Retapamulin, also known as SB-275833, is a newer topical agent of pleuromutilin class approved by the Food and Drug Administration for treatment of impetigo in children. It has been demonstrated to have low potential for the development of antibacterial resistance and a high degree of potency against poly drug resistant Gram-positive bacteria found in skin infections including Staphylococcus aureus strains. The drug is safe owing to low systemic absorption and has only minimal side-effect of local irritation at the site of application.
Synonyms
SB-275833; SB 275833; SB275833; Retapamulin, brand names Altabax and Altargo
IUPAC Name
(3aR,4S,5R,7S,8S,9R,9aS,12R)-8-hydroxy-4,7,9,12-tetramethyl-3-oxo-7-vinyldecahydro-4,9a-propanocyclopenta[8]annulen-5-yl 2-(((1R,3s,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl)thio)acetate
Canonical SMILES
O=C(O[C@@H]1C[C@](C=C)(C)[C@@H](O)[C@H](C)[C@]2(CCC3=O)[C@]3([H])[C@]1(C)[C@H](C)CC2)CS[C@@H]4C[C@@](N5C)([H])CC[C@@]5([H])C4
InChI
InChI=1S/C30H47NO4S/c1-7-28(4)16-24(35-25(33)17-36-22-14-20-8-9-21(15-22)31(20)6)29(5)18(2)10-12-30(19(3)27(28)34)13-11-23(32)26(29)30/h7,18-22,24,26-27,34H,1,8-17H2,2-6H3/t18-,19+,20-,21+,22-,24-,26+,27+,28-,29-,30+/m1/s1
InChI Key
STZYTFJPGGDRJD-QPCPVAGTSA-N
Solubility
Soluble in DMSO
Appearance
White to off-white solid powder
Shelf Life
>2 years if stored properly
Storage
Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
Biological Target
Retapamulin(SB-275833) is a topical antibiotic, which binds to both E. coli and S. aureus ribosomes with similar potencies with Kd of 3 nM.
Drug Formulation
This drug may be formulated in DMSO
Elemental Analysis
C, 69.59; H, 9.15; N, 2.71; O, 12.36; S, 6.19
HS Tariff Code
2934.99.9001
In Vitro Activity
The purpose of this study was to determine the in vitro activity of retapamulin against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and linezolid and methicillin-resistant S. aureus.The minimum inhibitory concentrations (MICs) were determined on Mueller-Hinton agar. Retapamulin inhibited all the isolates of MSSA and MRSA at 0.125 mg/L, but the 18 linezolid-resistant-MRSA strains proved resistant, with MICs over 32 mg/L. Retapamulin demonstrated excellent in vitro activity against MSSA and MRSA strains, but not against MRSA isolates harbouring the cfr gene. The results of this in vitro study support cut-off values for retapamulin of ≤ 0.5, 1, and ≥ 2 mg/L for susceptible, intermediate, and resistant strains, respectively.
Reference: Rev Esp Quimioter. 2011 Sep;24(3):127-30. https://pubmed.ncbi.nlm.nih.gov/21947094/
In Vivo Activity
The purpose of this study was to evaluate the effect of topically applied retapamulin ointment using various dosing regimens in the Staphylococcus aureus and Streptococcus pyogenes wound infection model. Therapy was administered topically (0.1 ml/mouse) b.i.d. (beginning at 1 and 7 h postinfection) or t.i.d. (beginning at 1, 4, and 7 h postinfection) and continued for 3, 4, or 6 days (4, 5, or 7 days of therapy). Additional groups of mice received petrolatum ointment or remained untreated to act as placebo or infected controls. Following infection with S. aureus J1225 (5 days postinfection), bacterial numbers from untreated control animals were 6.3 ± 0.3 log10 CFU/wound. Retapamulin administered t.i.d. for 4 days demonstrated significant efficacy (P ≤ 0.01) compared with untreated animals at all concentrations tested. A maximum 4.6 log10 reduction in bacterial counts was achieved at 2% (wt/wt) (1.7 ± 0.1 log10 CFU/wound; 7/8 wounds cleared to the limit of detection). All retapamulin concentrations evaluated produced a potent effect compared with untreated or placebo-treated animals (P ≤ 0.01). The effect obtained with 4-day t.i.d. application of 0.5%, 1%, and 2% wt/wt were similar, reducing bacterial counts by >5 log10 (1.9 ± 0.4, 2.3 ± 1.3, and 2.3 ± 1.5 log10 CFU/wound, respectively). Overall, these results demonstrate the potential benefit of retapamulin over existing topical antibiotics, particularly against isolates resistant to currently used agents.
Reference: Antimicrob Agents Chemother. 2006 Nov; 50(11): 3886-3888. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1635196/
Shipping
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.
Stock Solution Storage
0-4 °C for short term (days to weeks), or -20 °C for long term (months).