Daptomycin
[CAS# 103060-53-3]

Identification

• Classification: API >> Synthetic anti-infective drugs >> Antifungal drugs
• Name: Daptomycin
• Synonyms: (3S)-3-[[(2R)-4-amino-2-[[(2S)-2-(decanoylamino)-3-(1H-indol-3-yl)propanoyl]amino]-4-oxobutanoyl]amino]-4-[[(3S,6S,9R,15S,18R,21S,24S,30S,31R)-3-[2-(2-aminophenyl)-2-oxoethyl]-24-(3-aminopropyl)-15,21-bis(carboxymethyl)-6-[(2R)-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-nonazacyclohentriacont-30-yl]amino]-4-oxobutanoic acid
• Molecular Formula: C₇₂H₁₀₁N₁₇O₂₆
• Molecular Weight: 1620.67
• CAS Registry Number: 103060-53-3
• EC Number: 600-389-2
• SMILES: CCCCCCCCCC(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@H](CC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H]3[C@H](OC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC3=O)CCCN)CC(=O)O)C)CC(=O)O)CO)[C@H](C)CC(=O)O)CC(=O)C4=CC=CC=C4N)C

Properties

• Density: 1.5±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.638, Calc.^*
• Boiling Point: 2078.2±65.0 °C (760 mmHg), Calc.^*
• Flash Point: 1210.7±34.3 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS08 Warning
• Risk Statements: H373
• Safety Statements: P260-P319-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Skin sensitization	Skin Sens.	1	H317
Acute toxicity	Acute Tox.	3	H311
Acute toxicity	Acute Tox.	4	H302

Discovery and Applications

Daptomycin, a cyclic lipopeptide antibiotic, was discovered in the late 1980s by scientists at Eli Lilly and Company through screening microbial extracts for novel antimicrobial compounds. It was isolated from cultures of Streptomyces roseosporus, a soil bacterium found to produce a compound with potent antimicrobial activity against gram-positive bacteria. Daptomycin's unique mechanism of action involves disrupting bacterial cell membrane function, leading to rapid cell death.

Daptomycin is indicated for the treatment of complicated skin and soft tissue infections (SSTIs) caused by susceptible gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). These infections, which range from cellulitis and abscesses to surgical wound infections, pose significant clinical challenges due to the increasing prevalence of antibiotic resistance. Daptomycin is used for the treatment of bloodstream infections (BSIs) caused by gram-positive pathogens, including Staphylococcus aureus, Enterococcus faecalis, and Streptococcus species. It is particularly effective in cases of bacteremia and endocarditis, where rapid bactericidal activity and deep tissue penetration are essential for successful treatment outcomes. Daptomycin is employed in the management of osteomyelitis, a bone infection often caused by Staphylococcus aureus, including MRSA strains. It is also used in the treatment of infective endocarditis, a serious infection of the heart valves commonly caused by virulent gram-positive bacteria. Daptomycin's bactericidal activity and ability to penetrate biofilms make it a valuable therapeutic option in these challenging infections. Daptomycin is indicated for the treatment of pneumonia caused by gram-positive pathogens, including MRSA and Streptococcus pneumoniae. It is used in both community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP), providing an alternative to traditional antibiotics for patients with suspected or confirmed gram-positive pneumonia.

References

2005. Daptomycin, a new drug class for the treatment of Gram-positive infections. Drugs of Today, 41(2).
DOI: 10.1358/dot.2005.41.2.882660

2012. Prevention of Vascular Graft Infections with Antibiotic Graft Impregnation Prior to Implantation: In Vitro Comparison between Daptomycin, Rifampin and Nebacetin. European Journal of Vascular and Endovascular Surgery, 43(4).
DOI: 10.1016/j.ejvs.2011.12.029

2024. Structure Elucidation of the Daptomycin Products Generated upon Heterologous Expression of the Daptomycin Resistance Gene Cluster drcAB. ACS Infectious Diseases, 10(12).
DOI: 10.1021/acsinfecdis.4c00637