WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 598541
CAS#: 1350636-82-6 (acetate)
Description: Lefamulin, also known as BC-3781, is the primary pleuromutilin antibiotic which has been used for both intravenous and oral use for the remedy of bacterial infections. It has shown activity against gram-positive bacteria including methicillin-resistant strains as well as atypical organisms which as often implicated in CABP. It has a completely unique mechanism of action that inhibits protein synthesis via way of means of stopping the binding of tRNA for peptide transfer. The C(14) side chain is responsible for its pharmacodynamic and antimicrobial properties, together with supporting in overcoming bacterial ribosomal resistance and mutations improvement amplifying the number of hydrogen bonds to the target site. Lefamulin was approved in 2019.
MedKoo Cat#: 598541
Name: Lefamulin acetate
CAS#: 1350636-82-6 (acetate)
Chemical Formula: C30H49NO7S
Exact Mass:
Molecular Weight: 567.782
Elemental Analysis: C, 63.46; H, 8.70; N, 2.47; O, 19.72; S, 5.65
Related CAS #: 1061337-51-6 (free base) 1350636-82-6 (acetate)
Synonym: Lefamulin acetate; BC-3781.Ac; BC 3781.Ac; BC3781.Ac; BC-3781; BC 3781; BC3781; Xenleta;
IUPAC/Chemical Name: (3aR,4R,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,2R,4R)-4-amino-2-hydroxycyclohexyl)thio)acetate acetic acid (1:1)
InChi Key: WSMXIQXWHPSVDE-ZPJPNJFZSA-N
InChi Code: InChI=1S/C28H45NO5S.C2H4O2/c1-6-26(4)14-22(34-23(32)15-35-21-8-7-18(29)13-20(21)31)27(5)16(2)9-11-28(17(3)25(26)33)12-10-19(30)24(27)28;1-2(3)4/h6,16-18,20-22,24-25,31,33H,1,7-15,29H2,2-5H3;1H3,(H,3,4)/t16-,17+,18-,20-,21-,22-,24+,25+,26-,27+,28+;/m1./s1
SMILES Code: CC(O)=O.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]4[C@H](O)C[C@H](N)CC4
Appearance: Solid powder
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
Shelf Life: >3 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
| Biological target: | Lefamulin acetate (BC-3781 acetate) inhibits protein synthesis by binding to the peptidyl transferase center of the 50S bacterial ribosome, preventing the binding of transfer RNA for peptide transfer. |
| In vitro activity: | The pleuromutilin antibiotic lefamulin demonstrated in vitro activity against the most relevant bacterial pathogens causing sexually transmitted infections (STI), including Chlamydia trachomatis (MIC50/90, 0.02/0.04 mg/liter; n = 15), susceptible and multidrug-resistant Mycoplasma genitalium (MIC range, 0.002 to 0.063 mg/liter; n = 6), and susceptible and resistant Neisseria gonorrhoeae (MIC50/90, 0.12/0.5 mg/liter; n = 25). The results suggest that lefamulin could be a promising first-line antibiotic for the treatment of STI, particularly in populations with high rates of resistance to standard-of-care antibiotics. Reference: Antimicrob Agents Chemother. 2018 Apr 26;62(5):e02380-17. https://pubmed.ncbi.nlm.nih.gov/29530863/ |
| In vivo activity: | In the in vivo mouse lung neutrophilia model, lefamulin treatment at doses of 10, 30, and 100 mg/kg SC at 30 minutes before intranasal LPS challenge (30 minutes pretreatment) was associated with a dose-dependent reduction in total cell and neutrophil recruitment to the lungs (measured in BALF) at 4 hours postchallenge compared with the vehicle control group. These reductions were comparable to those observed following treatment with 1 mg/kg IP dexamethasone, with a tendency toward more potent inhibition of total cell counts and neutrophil cell counts at the highest lefamulin dose of 100 mg/kg. Pretreatment with azithromycin at doses of 10, 30, and 100 mg/kg SC demonstrated significant dose-dependent reductions in total cell and neutrophil counts as well, although the effects on neutrophil counts in BALF were more pronounced with the 30- and 100-mg/kg lefamulin doses. Similar results were observed in an independent experiment using higher doses of lefamulin and azithromycin. Reference: PLoS One. 2021 Sep 29;16(9):e0237659. https://pubmed.ncbi.nlm.nih.gov/34587166/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 100.0 | 176.12 |
The following data is based on the product molecular weight 567.782 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 |
| Formulation protocol: | 1. Paukner S, Gruss A, Jensen JS. In Vitro Activity of Lefamulin against Sexually Transmitted Bacterial Pathogens. Antimicrob Agents Chemother. 2018 Apr 26;62(5):e02380-17. doi: 10.1128/AAC.02380-17. PMID: 29530863; PMCID: PMC5923106. 2. Hafner M, Paukner S, Wicha WW, Hrvačić B, Cedilak M, Faraho I, Gelone SP. Anti-inflammatory activity of lefamulin versus azithromycin and dexamethasone in vivo and in vitro in a lipopolysaccharide-induced lung neutrophilia mouse model. PLoS One. 2021 Sep 29;16(9):e0237659. doi: 10.1371/journal.pone.0237659. PMID: 34587166; PMCID: PMC8480901. |
| In vitro protocol: | 1. Paukner S, Gruss A, Jensen JS. In Vitro Activity of Lefamulin against Sexually Transmitted Bacterial Pathogens. Antimicrob Agents Chemother. 2018 Apr 26;62(5):e02380-17. doi: 10.1128/AAC.02380-17. PMID: 29530863; PMCID: PMC5923106. 2. Hafner M, Paukner S, Wicha WW, Hrvačić B, Cedilak M, Faraho I, Gelone SP. Anti-inflammatory activity of lefamulin versus azithromycin and dexamethasone in vivo and in vitro in a lipopolysaccharide-induced lung neutrophilia mouse model. PLoS One. 2021 Sep 29;16(9):e0237659. doi: 10.1371/journal.pone.0237659. PMID: 34587166; PMCID: PMC8480901. |
| In vivo protocol: | 1. Hafner M, Paukner S, Wicha WW, Hrvačić B, Cedilak M, Faraho I, Gelone SP. Anti-inflammatory activity of lefamulin versus azithromycin and dexamethasone in vivo and in vitro in a lipopolysaccharide-induced lung neutrophilia mouse model. PLoS One. 2021 Sep 29;16(9):e0237659. doi: 10.1371/journal.pone.0237659. PMID: 34587166; PMCID: PMC8480901. |
1: Tang HJ, Lai CC. Lefamulin for treating community-acquired bacterial pneumonia in adult patients aged < 65 years. Clin Infect Dis. 2019 Dec 11. pii: ciz1173. doi: 10.1093/cid/ciz1173. [Epub ahead of print] PubMed PMID: 31822903.
2: Lee YR, Jacobs KL. Leave it to Lefamulin: A Pleuromutilin Treatment Option in Community-Acquired Bacterial Pneumonia. Drugs. 2019 Nov;79(17):1867-1876. doi: 10.1007/s40265-019-01219-5. Review. PubMed PMID: 31705486.
3: Lefamulin (Xenleta) for Community-Acquired Bacterial Pneumonia. JAMA. 2019 Nov 5;322(17):1709-1710. doi: 10.1001/jama.2019.16482. PubMed PMID: 31688883.
4: File TM, Goldberg L, Das A, Sweeney C, Saviski J, Gelone SP, Seltzer E, Paukner S, Wicha WW, Talbot GH, Gasink LB. Efficacy and Safety of Intravenous-to-oral Lefamulin, a Pleuromutilin Antibiotic, for the Treatment of Community-acquired Bacterial Pneumonia: The Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial. Clin Infect Dis. 2019 Oct 18. pii: ciz710. doi: 10.1093/cid/ciz710. [Epub ahead of print] PubMed PMID: 31626688.
5: Lefamulin (Xenleta) for community-acquired bacterial pneumonia. Med Lett Drugs Ther. 2019 Sep 23;61(1581):145-148. Review. PubMed PMID: 31599865.
6: Alexander E, Goldberg L, Das AF, Moran GJ, Sandrock C, Gasink LB, Spera P, Sweeney C, Paukner S, Wicha WW, Gelone SP, Schranz J. Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia: The LEAP 2 Randomized Clinical Trial. JAMA. 2019 Sep 27. doi: 10.1001/jama.2019.15468. [Epub ahead of print] PubMed PMID: 31560372.
7: Malani PN. Lefamulin-A New Antibiotic for Community-Acquired Pneumonia. JAMA. 2019 Sep 27. doi: 10.1001/jama.2019.16215. [Epub ahead of print] PubMed PMID: 31560367.
8: Koulenti D, Xu E, Yin Sum Mok I, Song A, Karageorgopoulos DE, Armaganidis A, Lipman J, Tsiodras S. Lefamulin. Comment on: "Novel Antibiotics for Multidrug-Resistant Gram-Positive Microorganisms. Microorganisms, 2019, 7, 270". Microorganisms. 2019 Sep 24;7(10). pii: E386. doi: 10.3390/microorganisms7100386. PubMed PMID: 31554342; PubMed Central PMCID: PMC6843636.
9: Perry W, Golan Y. Therapeutic potential of lefamulin in the treatment of community-acquired pneumonia. Future Microbiol. 2019 Jul;14:927-939. doi: 10.2217/fmb-2019-0027. Epub 2019 Jul 23. PubMed PMID: 31333062.
10: Rodvold KA. Introduction: lefamulin and pharmacokinetic/pharmacodynamic rationale to support the dose selection of lefamulin. J Antimicrob Chemother. 2019 Apr 1;74(Supplement_3):iii2-iii4. doi: 10.1093/jac/dkz084. PubMed PMID: 30949709; PubMed Central PMCID: PMC6449571.
11: Zhang L, Wicha WW, Bhavnani SM, Rubino CM. Prediction of lefamulin epithelial lining fluid penetration after intravenous and oral administration using Phase 1 data and population pharmacokinetics methods. J Antimicrob Chemother. 2019 Apr 1;74(Supplement_3):iii27-iii34. doi: 10.1093/jac/dkz088. PubMed PMID: 30949708; PubMed Central PMCID: PMC6449575.
12: Wicha WW, Strickmann DB, Paukner S. Pharmacokinetics/pharmacodynamics of lefamulin in a neutropenic murine pneumonia model with Staphylococcus aureus and Streptococcus pneumoniae. J Antimicrob Chemother. 2019 Apr 1;74(Supplement_3):iii11-iii18. doi: 10.1093/jac/dkz086. PubMed PMID: 30949707; PubMed Central PMCID: PMC6449573.
13: Wicha WW, Craig WA, Andes D. In vivo pharmacodynamics of lefamulin, the first systemic pleuromutilin for human use, in a neutropenic murine thigh infection model. J Antimicrob Chemother. 2019 Apr 1;74(Supplement_3):iii5-iii10. doi: 10.1093/jac/dkz085. PubMed PMID: 30949706; PubMed Central PMCID: PMC6449574.
14: Bhavnani SM, Zhang L, Hammel JP, Rubino CM, Bader JC, Sader HS, Gelone SP, Wicha WW, Ambrose PG. Pharmacokinetic/pharmacodynamic target attainment analyses to support intravenous and oral lefamulin dose selection for the treatment of patients with community-acquired bacterial pneumonia. J Antimicrob Chemother. 2019 Apr 1;74(Supplement_3):iii35-iii41. doi: 10.1093/jac/dkz089. PubMed PMID: 30949705; PubMed Central PMCID: PMC6449570.
15: Wicha WW, Prince WT, Lell C, Heilmayer W, Gelone SP. Pharmacokinetics and tolerability of lefamulin following intravenous and oral dosing. J Antimicrob Chemother. 2019 Apr 1;74(Supplement_3):iii19-iii26. doi: 10.1093/jac/dkz087. PubMed PMID: 30949704; PubMed Central PMCID: PMC6449572.
16: File TM, Goldberg L, Das A, Sweeney C, Saviski J, Gelone SP, Seltzer E, Paukner S, Wicha WW, Talbot GH, Gasink LB. Efficacy and Safety of Intravenous-to-oral Lefamulin, a Pleuromutilin Antibiotic, for the Treatment of Community-acquired Bacterial Pneumonia: The Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial. Clin Infect Dis. 2019 Nov 13;69(11):1856-1867. doi: 10.1093/cid/ciz090. PubMed PMID: 30722059; PubMed Central PMCID: PMC6853694.
17: Mendes RE, Paukner S, Doyle TB, Gelone SP, Flamm RK, Sader HS. Low Prevalence of Gram-Positive Isolates Showing Elevated Lefamulin MIC Results during the SENTRY Surveillance Program for 2015-2016 and Characterization of Resistance Mechanisms. Antimicrob Agents Chemother. 2019 Mar 27;63(4). pii: e02158-18. doi: 10.1128/AAC.02158-18. Print 2019 Apr. PubMed PMID: 30670418; PubMed Central PMCID: PMC6437497.
18: Paukner S, Gelone SP, Arends SJR, Flamm RK, Sader HS. Antibacterial Activity of Lefamulin against Pathogens Most Commonly Causing Community-Acquired Bacterial Pneumonia: SENTRY Antimicrobial Surveillance Program (2015-2016). Antimicrob Agents Chemother. 2019 Mar 27;63(4). pii: e02161-18. doi: 10.1128/AAC.02161-18. Print 2019 Apr. PubMed PMID: 30670415; PubMed Central PMCID: PMC6437505.
19: Dillon C, Guarascio AJ, Covvey JR. Lefamulin: a promising new pleuromutilin antibiotic in the pipeline. Expert Rev Anti Infect Ther. 2019 Jan;17(1):5-15. doi: 10.1080/14787210.2019.1554431. Epub 2018 Dec 7. Review. PubMed PMID: 30513017.
20: Veve MP, Wagner JL. Lefamulin: Review of a Promising Novel Pleuromutilin Antibiotic. Pharmacotherapy. 2018 Sep;38(9):935-946. doi: 10.1002/phar.2166. Epub 2018 Aug 20. Review. PubMed PMID: 30019769.
