Lipopeptide
Bacterial cell membrane phospholipids (calcium-dependent binding; MIC range for Gram-positive bacteria: 0.06-4 μg/mL, varies by bacterial species) [1]
- No specific enzyme or receptor targets; antimicrobial activity via disruption of bacterial membrane integrity [2]

Daptomycin (5 μg/ml) in 30 minutes decreases Staphylococcus aureus cell viability by >99% and membrane potential by >90%. Hemolytic streptococci, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci are among the clinically significant strains of gram-positive pathogens against which daptomycin demonstrates rapid in vitro bactericidal activity. As shown by studies on binding and fractionation, daptomycin acts at the cytoplasmic membrane of susceptible bacteria (8). Furthermore, daptomycin is not the same as some antimicrobial peptides (such as human neutrophil peptide 1), which can depolarize the cytoplasmic membrane quickly but do not cause cell death for one to two hours. Whole-cell and artificial membrane studies have shown that daptomycin inserts into the cytoplasmic membrane of bacteria.[1] Daptomycin kills ≥3 log CFU/ml by 8 hours, demonstrating higher bactericidal activity than all other drugs tested. A member of the peptolide (acid lipopeptide antibiotic) class of antimicrobial agents, daptomycin is a cyclic polypeptide that is obtained from Streptomyces roseosporus. Additionally effective against gram-positive bacteria resistant to vancomycin, such as enterococci, is daptomycin. Daptomycin exhibits a high degree of protein binding (94%), and its in vitro activity is influenced by serum or albumin.[2] The lipophilic Daptomycin tail enters the bacterial cell membrane quickly, resulting in membrane depolarization and potassium ion efflux. Daptomycin is a 13-member amino acid cyclic lipopeptide with a decanoyl side-chain. Treatment with daptomycin has been associated with skeletal muscle toxicity that is fully reversible, but has no effect on cardiac or smooth muscle.[3]

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Exhibited potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains with MIC values of 0.125-1 μg/mL (microbroth dilution assay, 24-hour incubation at 37°C); inhibited bacterial growth by >99% at 2×MIC [1]
- Active against vancomycin-resistant Enterococcus faecium (VRE) with MIC range of 0.25-2 μg/mL; maintained activity against vancomycin-intermediate S. aureus (VISA) with MIC=0.5 μg/mL [3]
- Disrupted membrane integrity of S. aureus ATCC 29213: 1 μg/mL treatment for 1 hour increased membrane permeability, as evidenced by uptake of propidium iodide (PI) by 75% compared to untreated controls; led to bacterial cell lysis within 4 hours [2]
- Inhibited biofilm formation of MRSA on polystyrene surfaces; 0.5 μg/mL Daptomycin (LY146032) reduced biofilm biomass by 60% after 48-hour incubation [4]
- No activity against Gram-negative bacteria (e.g., Escherichia coli, Pseudomonas aeruginosa) with MIC >32 μg/mL due to outer membrane barrier [5]

Daptomycin showed linear pharmacokinetics, with a half-life of 0.9 to 1.4 hours and an area under the concentration-time curve (AUC) of 9.4 from time zero to infinity/dose. Ninety percent of the protein bound [5].

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Protected mice against MRSA-induced sepsis; intravenous (i.v.) administration of 10 mg/kg every 12 hours for 3 days resulted in 85% survival rate, compared to 20% in vehicle control; reduced bacterial load in blood by 4 log10 CFU/mL [1]
- Inhibited skin infection caused by S. aureus in hairless mice; subcutaneous (s.c.) dosing of 5 mg/kg daily for 5 days reduced lesion size by 70% and cleared bacteria from the infection site (undetectable CFU in tissue homogenates) [3]
- Efficacious in a rat model of VRE-induced endocarditis; i.v. injection of 15 mg/kg once daily for 7 days reduced bacterial counts in heart valves by 3 log10 CFU/g compared to untreated rats [4]

Performed microbroth dilution assay to determine MIC values: inoculated cation-adjusted Mueller-Hinton broth (CAMHB) with Gram-positive bacteria (1×105 CFU/mL) in 96-well plates; added Daptomycin (LY146032) at concentrations of 0.015-32 μg/mL; incubated at 37°C for 24 hours; MIC was defined as the lowest concentration inhibiting visible bacterial growth [1]
- Assessed membrane permeability: cultured S. aureus ATCC 29213 in CAMHB to mid-log phase; treated with 0.25-4 μg/mL Daptomycin (LY146032) and 10 μM PI; incubated at 37°C with shaking; measured PI fluorescence intensity at 535 nm/617 nm (excitation/emission) at 1-hour intervals for 4 hours [2]
- Evaluated biofilm inhibition: seeded MRSA (1×104 CFU/mL) in 96-well polystyrene plates; added Daptomycin (LY146032) (0.125-2 μg/mL) and incubated at 37°C for 48 hours; removed planktonic bacteria, fixed biofilms with methanol, stained with crystal violet; quantified biofilm biomass by absorbance at 570 nm [4]

20 mg/kg; s.c.
After an 18-hour brain heart infusion broth culture, inocula with 109 CFU/mL are prepared. Finally, the conventional serial 10-fold dilution agar pour plate method is used to ascertain the precise number in each inoculum. Using an intravenous 1.0 mL inoculum, animals are challenged. Rats with normal kidney function have been shown to be infected by this inoculum. After twenty-four hours, the animals are split up into eight groups and given either saline only (controls) or antibiotic therapy starting with 10 mg/kg of Daptomycin, 20 mg/kg of Daptomycin, Daptomycin 10 plus gentamicin at 1.5 mg/kg, 20 mg/kg of vancomycin, 20 mg/kg of vancomycin plus gentamicin at 1.5 mg/kg, 30 mg of ampicillin per rat per injection, and 30 mg of ampicillin per rat plus 1.5 mg/kg of gentamicin. Daptomycin20 is given to animals once daily; all other medications are given twice a day. Ampicillin and gentamicin are injected intramuscularly; vancomycin and daptomycin are administered subcutaneously. Medication is given for a maximum of thirteen days.

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Mouse sepsis model: CD-1 mice (6-8 weeks old) were inoculated intraperitoneally (i.p.) with 5×107 CFU of MRSA; 1 hour post-inoculation, mice received i.v. injection of Daptomycin (LY146032) (dissolved in 0.9% normal saline) at 5, 10, or 20 mg/kg, followed by additional doses every 12 hours for 3 days; control mice received normal saline; survival was monitored for 7 days, and blood bacterial load was quantified at 24 hours post-treatment [1]
- Mouse skin infection model: Hairless mice (8-10 weeks old) were inoculated intradermally (i.d.) with 1×106 CFU of S. aureus on the dorsal skin; 24 hours post-inoculation, Daptomycin (LY146032) (suspended in 0.5% carboxymethylcellulose sodium) was administered s.c. at 5 mg/kg daily for 5 days; lesion size was measured daily, and tissue bacterial load was determined at sacrifice [3]
- Rat endocarditis model: Sprague-Dawley rats (250-300 g) were surgically implanted with a catheter to induce endocarditis, then inoculated i.v. with 1×108 CFU of VRE; 24 hours post-inoculation, rats received i.v. Daptomycin (LY146032) (dissolved in phosphate-buffered saline) at 15 mg/kg once daily for 7 days; control rats received buffer alone; heart valves were harvested to quantify bacterial counts [4]

Absorption, Distribution and Excretion
Daptomycin was administered once daily to healthy volunteers via intravenous infusion over 30 minutes at doses of 4, 6, 8, 10, and 12 mg/kg. Results showed Cmax values between 57.8 ± 3.0 and 183.7 ± 25.0 μg/mL, and AUC0-24 values between 494 ± 75 and 1277 ± 253 μg/mL. The pharmacokinetics of daptomycin were generally linear, but some changes were observed at doses exceeding 6 mg/kg, with steady-state Cmax and AUC values approximately 20% higher than initial values, suggesting some accumulation. After three daily doses, steady-state trough concentrations ranged between 5.9 ± 1.6 and 13.7 ± 5.2 μg/mL. Data from a single intravenous injection of daptomycin 6 mg/kg (administered over 30 minutes) were used to estimate the steady-state Cmax values for 4 mg/kg and 6 mg/kg doses (administered over 2 minutes), which were 77.7 ± 8.1 μg/mL and 116.6 ± 12.2 μg/mL, respectively. Cmax could not be determined for intravenous daptomycin (4 mg/kg or 6 mg/kg, administered over 2 minutes), but steady-state AUC values were obtained, which were 475 ± 71 μg/mL and 701 ± 82 μg/mL, respectively. The mean steady-state AUC values in patients with severe renal impairment and those on dialysis were approximately 2–3 times higher than those in patients with normal renal function. No clinically significant differences in daptomycin pharmacokinetics were observed in patients with mild to moderate hepatic impairment. In healthy older adults (75 years and older), the mean AUC0-∞ value was approximately 58% higher than in healthy younger controls, while the Cmax value was not different. The AUC0-∞ value was also approximately 30% higher in obese patients. In pediatric patients, no significant differences in Cmax or AUC values adjusted for weight and age were observed. Daptomycin is primarily excreted by the kidneys, with approximately 78% of the administered dose excreted in the urine and only 5.7% in the feces. Approximately 52% of the dose excreted in the urine retains antibacterial activity. The volume of distribution of daptomycin is very small, averaging approximately 0.1 L/kg in healthy adults, and is dose-independent. The volume of distribution tends to increase with declining renal function, estimated at approximately 0.2 L/kg in patients with severe renal impairment. With once-daily intravenous infusion of daptomycin at doses of 4, 6, 8, 10, and 12 mg/kg over 30 minutes, total plasma clearance in healthy volunteers ranged from 7.2 ± 1.1 to 9.6 ± 1.3 mL/h/kg, showing no significant dose-related correlation. Because daptomycin is primarily excreted by the kidneys, total plasma clearance was 9%, 22%, and 46% lower in patients with mild, moderate, and severe renal impairment, respectively, compared to healthy controls. Daptomycin clearance was also lower in obese patients (reduced by 15-23%) and elderly patients (35% lower in patients aged 75 years and older), while clearance was often higher in children, even after adjusting for weight. Metabolites/Metabolites: Inactive metabolites were detected in the urine of five healthy adults after administration of radiolabeled daptomycin. Another study in healthy adults using 6 mg/kg daptomycin showed trace amounts of three oxidative metabolites and one unidentified metabolite in the urine, but none were detected in plasma. The site of metabolism is unclear because studies using human hepatocytes have shown that daptomycin interacts minimally with the various CYP450 enzymes present in the liver.

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Biological Half-Life
Daptomycin has a relatively long half-life, ranging from 7.5 to 9 hours depending on the dosing regimen and dose intensity. The half-life prolongs with increasing renal impairment; the half-life is 27.83 ± 14.85 hours for patients with creatinine clearance <30 mL/min, 30.51 ± 6.51 hours for hemodialysis patients, and 27.56 ± 4.53 hours for patients on continuous ambulatory peritoneal dialysis (CAPD). The half-life of daptomycin also tends to shorten with age.

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After intravenous injection of 10 mg/kg daptomycin (LY146032) into rats, the plasma half-life (t1/2) is 2.5 hours; the volume of distribution (Vd) is 0.2 L/kg [5]
-In humans, the plasma half-life is 8-10 hours; the plasma protein binding rate is 90-95% [1]
-Oral bioavailability in dogs and humans is <1%; administered only via parenteral route (intravenous or subcutaneous) [2]
-Mainly excreted unchanged in urine; 70-80% of the dose is recovered in urine within 48 hours [5]
-No significant metabolism was observed in liver microsomes in rats, dogs, or humans [5]

Hepatotoxicity
In patients receiving daptomycin, 2% to 6% experience elevated serum transaminase levels, a slightly higher incidence than in placebo or control patients. These elevations are usually mild to moderate, asymptomatic, and self-limiting, typically resolving spontaneously without discontinuation of treatment. Case reports of daptomycin potentially causing liver injury exist, but in most cases, serum bilirubin levels are normal, and the elevations in serum transaminases are mild to moderate, often accompanied by severe muscle damage and significantly elevated creatine kinase (CK). Such cases without jaundice or elevated alkaline phosphatase are more likely due to muscle damage than liver injury. Nevertheless, a few cases have been reported with mild jaundice, accompanied by hepatocellular serum enzyme elevations, but normal CK levels. The incubation period is 5 weeks, without immune hypersensitivity or autoimmune features, and the resolution is slow, with mild abnormalities remaining after 6 weeks. Therefore, daptomycin can cause clinically apparent liver injury, but this is very rare. Probability Score: C (Possibly a cause of clinically apparent liver injury).

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Effects during pregnancy and lactation>
◉ Overview of use during lactation
Limited and slightly inconsistent information suggests that the concentration of daptomycin in breast milk is very low and is not expected to have any adverse effects on breastfed infants. No special precautions are required.
◉ Effects on breastfed infants
One lactating mother (lack of breastfeeding information) received intravenous daptomycin 500 mg and ertapenem 1 g once daily for 28 days due to pelvic infection. No adverse events occurred in the infant during treatment and follow-up examinations.
One lactating woman received intravenous daptomycin 500 mg once daily for 14 days. No adverse reactions occurred in the infant during treatment and for 7 days after the end of treatment.
◉ Effects on lactation and breast milk
No relevant published information was found as of the revision date.
Protein Binding
Daptomycin reversibly binds to plasma proteins, with a binding rate between 90-94%, independent of concentration. Although daptomycin primarily binds to serum albumin (HSA; 85-96%), it also binds to a considerable extent to α-1-acid glycoprotein (AGP; 25-51%). Surface plasmon resonance (SPR) experiments show that daptomycin can also bind to a variety of other plasma proteins, including α-1-antitrypsin, low-density lipoprotein (LDL), hemoglobin, sex hormone-binding globulin (SHBG), heme-binding protein, fibrinogen, α2-macroglobulin, β2-microglobulin, high-density lipoprotein (HDL), fibronectin, haptoglobulin, transferrin, and IgG. The main determinants of plasma binding are human serum albumin (HSA), α1-antitrypsin, LDL, SHBG, and heme-binding protein. Consistent with the observations of calculated volume of distribution, the protein binding rate of daptomycin decreased with declining renal function, approximately 88% in patients with creatinine clearance <30 mL/min, approximately 86% in hemodialysis patients, and approximately 84% in patients on continuous ambulatory peritoneal dialysis (CAPD).

[1]. Antimicrob Agents Chemother . 2003 Aug;47(8):2538-44.

[2]. Antimicrob Agents Chemother . 2000 Apr;44(4):1062-6.

[3]. Antimicrob Chemother . 2005 Mar;55(3):283-8.

[4]. Antimicrob Agents Chemother . 2001 Mar;45(3):845-51.

[5]. Antimicrob Agents Chemother . 2004 Jan;48(1):63-8.

Daptomycin is a polypeptide composed of N-decanoyltryptophan, asparagine, aspartic acid, threonine, glycine, ornithine, aspartic acid, D-alanine, aspartic acid, glycine, D-serine, threo-3-methylglutamic acid, and 3-anthraylalanine (also known as kynurenine) linked sequentially, forming a lactone through the condensation of the carboxyl group of 3-anthraylalanine with the alcohol group of a threonine residue. It is an antibacterial drug and a bacterial metabolite, belonging to the calcium-dependent antibiotic class. Daptomycin is a lipopeptide antibiotic, belonging to the macrolide, heterocyclic peptide, macrocyclic, and lipopeptide antibiotic classes. Daptomycin is a cyclic lipopeptide antibacterial agent with broad-spectrum antibacterial activity against Gram-positive bacteria, including methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA/MRSA) and vancomycin-resistant enterococci (VRE). The chemical structure of daptomycin consists of 13 amino acids, including several non-standard amino acids and D-amino acids. Its C-terminal 10 amino acids form an ester ring, and the N-terminal tryptophan is covalently linked to decanoic acid. Daptomycin was initially discovered in the early 1980s by researchers at Eli Lilly in soil samples from Mount Ararat in Turkey. Early development of daptomycin was temporarily halted due to observed myopathy, but was restarted in 1997 after Cubist Pharmaceuticals Inc. obtained a license for daptomycin; studies found that a once-daily dosing regimen reduced side effects while maintaining efficacy. Daptomycin was approved by the U.S. Food and Drug Administration (FDA) on September 12, 2003, and marketed by Cubist Pharmaceuticals LLC (Merck) under the brand name CUBICIN®. Daptomycin is a broad-spectrum antibiotic administered intravenously for the treatment of complicated skin and tissue infections, endocarditis, and bacteremia. Elevated serum enzymes during daptomycin treatment occur at a low to moderate rate, but rarely cause clinically significant liver damage. Data on the presence of cubimycin in Streptomyces filamentosus have been reported. Daptomycin is a semi-synthetic cyclic lipopeptide antibiotic isolated from Streptomyces roseosporus, exhibiting broad-spectrum antibacterial activity against Gram-positive bacteria. Its mechanism of action is unique: it binds to the bacterial cell membrane, causing rapid depolarization through calcium-dependent potassium ion efflux; this loss of membrane potential inhibits DNA, RNA, and protein synthesis, ultimately leading to bacterial death. The drug cannot penetrate the outer membrane of Gram-negative bacteria. A cyclic lipopeptide antibiotic that inhibits Gram-positive bacteria. See also: Daptomycin (note moved to).

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Indications
Daptomycin is indicated for the treatment of complicated skin and skin-soft tissue infections (cSSSI) in patients aged one year and older. It is also indicated for the treatment of Staphylococcus aureus bloodstream infections (bacteremia) in patients aged one year and older, including adult patients with right-sided infective endocarditis. Daptomycin is not indicated for the treatment of Staphylococcus aureus pneumonia or left-sided infective endocarditis. Due to potential effects on muscles, neuromuscular and/or the nervous system (including peripheral and/or central nervous systems), daptomycin is not recommended for use in children under one year of age. As with all antimicrobial agents, thorough testing is strongly recommended before initiating treatment to confirm that the infection is caused by susceptible bacteria. Otherwise, poor treatment response, treatment failure, and the development of drug-resistant bacteria may occur.
FDA Label
Daptomycin is indicated for the treatment of the following infections: complicated skin and soft tissue infections (cSSTI) in adults and children (1 to 17 years of age); right-sided infective endocarditis (RIE) caused by Staphylococcus aureus in adults. Antimicrobial susceptibility of the pathogen should be considered when deciding to use daptomycin, and should be based on expert opinion; Staphylococcus aureus bacteremia (SAB) in adults and children (1 to 17 years of age). Complicated skin and soft tissue infections (cSSTI) should be considered concurrently when using daptomycin in adults with bacteremia; cSSTI should be considered concurrently when using daptomycin in children with bacteremia. Daptomycin is effective only against Gram-positive bacteria. If a mixed infection with Gram-negative bacteria and/or certain types of anaerobic bacteria is suspected, daptomycin should be used in combination with an appropriate antibiotic. Guidelines for the rational use of antibiotics should be consulted. Daptomycin is indicated for the treatment of the following infections: complicated skin and soft tissue infections (cSSTI) in adults and children aged 1 to 17 years; and right-sided infective endocarditis (RIE) caused by Staphylococcus aureus in adults. Antimicrobial susceptibility of the pathogen should be considered and expert advice should be sought when deciding whether to use daptomycin. It is indicated for adults and children (1 to 17 years) with Staphylococcus aureus bacteremia (SAB). Adults with bacteremia should receive concurrent treatment for respiratory tract infection (RIE) or complicated skin and soft tissue infection (cSSTI) when using daptomycin; children with bacteremia should receive concurrent treatment for cSSTI when using daptomycin. Daptomycin is effective only against Gram-positive bacteria. If a mixed infection of Gram-negative bacteria and/or certain types of anaerobic bacteria is suspected, daptomycin should be used in combination with an appropriate antimicrobial agent. Guidelines for the rational use of antimicrobial agents should be consulted.

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Mechanism of Action
The mechanism of action of daptomycin is not fully understood. Studies have shown that it may directly inhibit the biosynthesis of cell membrane/cell wall components, including peptidoglycan, uridine diphosphate-N-acid, acetyl-L-alanine, and lipoteichoic acid (LTA). However, there is currently no convincing evidence to support these models, and other studies on Staphylococcus aureus and Enterococcus faecalis have ruled out the effect of daptomycin on LTA biosynthesis. It is well known that free daptomycin (de-co-daptomycin) is a trivalent anion at physiological pH, which binds to Ca²⁺ in a 1:1 stoichiometric ratio to form a monovalent anion. This process mainly depends on the Asp(7), Asp(9), and L-3MeGlu12 residues that constitute the DXDG motif. Because bacterial membranes are rich in acidic phospholipids—phosphatidylglycerol (PG) and cardiolipin (CL)—calcification promotes the preferential insertion of daptomycin into the bacterial membrane. It is hypothesized that daptomycin can bind two calcium ions in the bacterial membrane and form oligomers. Peptidoglycan (PG) is considered the main membrane component responsible for daptomycin's activity; daptomycin preferentially localizes in PG-rich membrane regions, and mutations affecting PG content are associated with daptomycin resistance. Calcium-dependent membrane binding is the currently accepted mechanism of action for daptomycin, but its exact downstream effects remain unclear, and several models have been proposed. One mechanism suggests that daptomycin membrane binding alters membrane fluidity, leading to the dissociation of cell wall biosynthetic enzymes (such as lipid II synthase MurG and phospholipid synthase PlsX). This is consistent with the effects of daptomycin on the cell morphology of various bacteria at concentrations equal to or above the minimum inhibitory concentration (MIC). Abnormal cell morphology is also consistent with the observed localization of daptomycin on the cell division septum and its hypothetical role in inhibiting cell division. A recent study showed that calcium-bound daptomycin, peptidoglycan (PG), and multiple undecylonitrile-coupled cell membrane precursors (subsequently containing lipid II) can form a ternary complex. This complex is thought to inhibit cell division, leading to the disruption of cell wall biosynthesis mechanisms and ultimately resulting in rupture of the septum bilayer, thus causing cell death. Another popular model is based on earlier observations that daptomycin causes potassium leakage and loss of membrane potential in treated bacterial cells in a calcium-dependent manner. Although this led some to believe that daptomycin might bind to peptidoglycan to form oligomeric pores on the bacterial membrane, cell lysis was not observed in Staphylococcus aureus or Enterococcus faecalis, and the daptomycin-induced ion transport was not consistent with pore formation. Instead, studies have proposed that daptomycin forms calcium-dependent dimer complexes in a fixed ratio of Dap₂Ca₃PG₂, which could act as transient ion carriers. The observed loss of membrane potential is thought to lead to a nonspecific loss of gradient-dependent nutrient transport, ATP production, and biosynthesis, ultimately resulting in cell death. It is noteworthy that these models are not entirely mutually exclusive and are supported to varying degrees by observed resistance mutations. Mutations in the mprF, cls2, pgsA, and dlt operons in Staphylococcus aureus, mutations in the cls gene in various enterococci, and mutations in pgsA, PG synthase, and the dlt operon in Escherichia coli all support the stringent PG requirement for daptomycin's bactericidal effect. These mutations in E. faecium alter the composition of the bacterial membrane, particularly the peptidoglycan (PG) content. Mutations in other regulatory systems controlling membrane homeostasis also suggest that the cell membrane is a site of action for daptomycin. Interestingly, in E. coli, these mutations alter the composition of the bacterial membrane, particularly the peptidoglycan content. Enterococcus faecalis, the most common daptomycin-resistant strain, is characterized by abnormal cell division septa, supporting a cell division-based mechanism of action for daptomycin.

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Daptomycin (LY146032) is a cyclic lipopeptide antibiotic derived from Streptomyces roseum[1].
- Its antibacterial mechanism involves calcium-dependent binding to bacterial cell membrane phospholipids, leading to membrane depolarization, pore formation, and cell lysis[2].
- It has been approved by the FDA for the treatment of complicated skin and soft tissue infections (cSSSI) and bloodstream infections (including sepsis) caused by Gram-positive bacteria[1].
- It remains active against vancomycin- or β-lactam-resistant Gram-positive pathogens (MRSA, VRE, VISA)[3].
- Its activity is enhanced at physiological calcium concentrations (1–2 mM)[5].

C72H101N17O26

1620.67

1619.71

C, 53.36; H, 6.28; N, 14.69; O, 25.67

103060-53-3

16134395

Off-white to light yellow solid powder

1.5±0.1 g/cm3

2078.2±65.0 °C at 760 mmHg

202-204?C

1210.7±34.3 °C

0.0±0.3 mmHg at 25°C

1.638

-4.07

22

28

35

115

3480

13

O1C(C([H])(C([H])([H])C(C2=C([H])C([H])=C([H])C([H])=C2N([H])[H])=O)N([H])C(C([H])(C([H])(C([H])([H])[H])C([H])([H])C(=O)O[H])N([H])C(C([H])(C([H])([H])O[H])N([H])C(C([H])([H])N([H])C(C([H])(C([H])([H])C(=O)O[H])N([H])C(C([H])(C([H])([H])[H])N([H])C(C([H])(C([H])([H])C(=O)O[H])N([H])C(C([H])(C([H])([H])C([H])([H])C([H])([H])N([H])[H])N([H])C(C([H])([H])N([H])C(C([H])(C1([H])C([H])([H])[H])N([H])C(C([H])(C([H])([H])C(=O)O[H])N([H])C(C([H])(C([H])([H])C(N([H])[H])=O)N([H])C(C([H])(C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12)N([H])C(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O

OAKLVKFURWEDJ-RWDRXURGSA-N

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

(3S)-3-[[(2S)-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

LY146032; LY 146032; Daptomycin; Cidecin; LY-146032; LY146032; trade name: Cubicin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (1.28 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (1.28 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (1.28 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (61.70 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)