Daptomycin

Daptomycin is a novel lipopeptide antibiotic used in the treatment of certain infections caused by Gram-positive organisms. It is a naturally occurring compound found in the soil saprotroph Streptomyces roseosporus. Its distinct mechanism of action means that it may be useful in treating infections caused by multi-resistant bacteria.

Product information

CAS Number: 103060-53-3

Molecular Weight: 1620.67

Formula: C72H101N17O26

Synonym:

Cidecin

Cubicin

LY-14603

LY 146032

LY146032

Chemical Name: 2, 2'-((3S, 6S, 9R, 15S, 18R, 21S, 24S)-30-((S)-2-((S)-4-amino-2-((S)-2-decanamido-3-(1H-indol-3-yl)propanamido)-4-oxobutanamido)-3-carboxypropanamido)-3-(2-(2-aminophenyl)-2-oxoethyl)-24-(3-aminopropyl)-6-((R)-1-carboxypropan-2-yl)-9-(hydroxymethyl)-18, 31-dimethyl-2, 5, 8, 11, 14, 17, 20, 23, 26, 29-decaoxo-1-oxa-4, 7, 10, 13, 16, 19, 22, 25, 28-nonaazacyclohentriacontane-15, 21-diyl)diacetic acid

Smiles: CCCCCCCCCC(=O)N[C@@H](CC1=CNC2=CC=CC=C12)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NC1C(C)OC(=O)[C@H](CC(=O)C2=CC=CC=C2N)NC(=O)[C@@H](NC(=O)[C@@H](CO)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCN)NC(=O)CNC1=O)[C@H](C)CC(O)=O

InChiKey: DOAKLVKFURWEDJ-AVSAZHKKSA-N

InChi: InChI=1S/C72H101N17O26/c1-5-6-7-8-9-10-11-22-53(93)81-44(25-38-31-76-42-20-15-13-17-39(38)42)66(108)84-45(27-52(75)92)67(109)86-48(30-59(102)103)68(110)89-61-37(4)115-72(114)49(26-51(91)40-18-12-14-19-41(40)74)87-71(113)60(35(2)24-56(96)97)88-69(111)50(34-90)82-55(95)32-77-63(105)46(28-57(98)99)83-62(104)36(3)79-65(107)47(29-58(100)101)85-64(106)43(21-16-23-73)80-54(94)33-78-70(61)112/h12-15,17-20,31,35-37,43-50,60-61,76,90H,5-11,16,21-30,32-34,73-74H2,1-4H3,(H2,75,92)(H,77,105)(H,78,112)(H,79,107)(H,80,94)(H,81,93)(H,82,95)(H,83,104)(H,84,108)(H,85,106)(H,86,109)(H,87,113)(H,88,111)(H,89,110)(H,96,97)(H,98,99)(H,100,101)(H,102,103)/t35-,36-,37?,43+,44+,45+,46+,47+,48+,49+,50-,60+,61?/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 100 mg/mL(61.7 mM). Water: 100 mg/mLwarmed(61.7 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Daptomycin (5 μg/ml) reduces cell viability by >99% and membrane potential by >90% within 30 min in Staphylococcus aureus. Daptomycin exhibits rapid in vitro bactericidal activity against clinically significant strains of gram-positive pathogens including hemolytic streptococci, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci. Daptomycin acts at the cytoplasmic membrane of susceptible bacteria (8), as demonstrated by binding and fractionation studies. Daptomycin also differs from that of some antimicrobial peptides (e.g., human neutrophil peptide 1) that are capable of rapid depolarization of the cytoplasmic membrane but do not induce cell death for 1 hour to 2 hours. Daptomycin inserts into the cytoplasmic membrane of bacteria, as indicated by whole-cell and artificial membrane studies. Daptomycin demonstrates greater bactericidal activity than all other drugs tested, killing ≥3 log CFU/ml by 8 hours. Daptomycin is a cyclic polypeptide derived from Streptomyces roseosporus and representing a class of antimicrobial agents known as the peptolides (acid lipopeptide antibiotics). Daptomycin is also active against vancomycin-resistant gram-positive bacteria, including enterococci. Daptomycin is highly protein bound (94%), and its in vitro activity is altered in the presence of serum or albumin. Daptomycin consists of a 13-member amino acid cyclic lipopeptide with a decanoyl side-chain, the lipophilic Daptomycin tail into the bacterial cell membrane, causing rapid membrane depolarization and a potassium ion efflux. Daptomycin treatment has been linked to fully reversible skeletal muscle toxicity with no effect on smooth or cardiac muscle.

In Vivo:

Daptomycin exhibited linear pharmacokinetics, with an area under the concentration-time curve (AUC) from time zero to infinity/dose of 9.4 and a half-life of 0.9 to 1.4 h. The level of protein binding was 90%.

References:

1. Silverman JA, et al. Antimicrob Agents Chemother, 2003, 47(8), 2538-2544.
2. Rybak MJ, et al. Antimicrob Agents Chemother, 2000, 44(4), 1062-1066.
3. Steenbergen JN, et al. J Antimicrob Chemother, 2005, 55(3), 283-288.
4. Louie A, et al. Antimicrob Agents Chemother. 2001, 45(3):845-51.
5. Safdar N, et al. Antimicrob Agents Chemother. 2004, 48(1):63-8

Products are for research use only. Not for human use.