| Size | Price | |
|---|---|---|
| 100mg | ||
| 250mg | ||
| 500mg |
| Targets |
(1→3)-β-D-glucan synthase
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|---|---|
| ln Vitro |
A sharp reduction of the metabolic activity of cells within the biofilm as assessed by the XTT reduction assay was demonstrated when preformed C. albicans 3153A biofilms were exposed to caspofungin (Fig.1). By this method, the 48-h MIC50 of caspofungin for sessile C. albicans 3153A cells within biofilms was 0.0625 μg/ml. Although complete sterility of biofilms was not achieved by treatment with caspofungin, the experiments showed a >97% reduction in the metabolic activity of sessile cells with caspofungin concentrations as low as 0.125 μg/ml. Caspofungin was also active against biofilms formed by all the C. albicans clinical isolates tested (n = 18), with MIC50s for sessile cells ranging between 0.0625 and 0.125 μg/ml, compared to fluconazole MIC50s for sessile cells of ≥64 μg/ml for all isolates. In agreement with the XTT assays, only residual metabolic activity was detected in cells within the caspofungin-treated biofilms, which showed a diffuse green fluorescence pattern characteristic of dead cells (Fig.3B). In confirmation of the SEM results, CLSM demonstrated that caspofungin treatment resulted in biofilms that were less hyphal and also showed minor distortions of the overall biofilm architecture. As shown in Fig.4, coating with caspofungin resulted in significant (up to 60%) reduction of the metabolic activity of adherent cells compared to that of cells in untreated (control) wells. Together these findings indicate that caspofungin displays potent activity against C. albicans biofilms in vitro and merits further investigation for the treatment of biofilm-associated infections. [3]
|
| ln Vivo |
Caspofungin (1-8 mg/kg; i.p.; daily for 7 days) enters the central nervous system of mice and reaches concentrations that diminish Candida burden in the brain [1]. Caspofungin (0.41-41 μM; i.p.; 5 weeks; male C57BL/6 mice) is a safe antifungal drug with mouse vitreous concentrations ranging from 0.41 to 4.1 μM [2].
|
| Enzyme Assay |
The echinocandin MK-0991, formerly L-743,872, is a water-soluble lipopeptide that has been demonstrated in preclinical studies to have potent activity against Candida spp., Aspergillus fumigatus, and Pneumocystis carinii. An extensive in vitro biological evaluation of MK-0991 was performed to better define the potential activities of this novel compound. Susceptibility testing with MK-0991 against approximately 200 clinical isolates of Candida, Cryptococcus neoformans, and Aspergillus isolates was conducted to determine MICs and minimum fungicidal concentrations MF(s). The MFC at which 90% of isolates are inhibited for 40 C. albicans clinical isolates was 0.5 microg/ml. Susceptibility testing with panels of antifungal agent-resistant species of Candida and C. neoformans isolates indicated that the MK-0991 MFCs for these isolates are comparable to those obtained for susceptible isolates. Growth kinetic studies of MK-0991 against Candida albicans and Candida tropicalis isolates showed that the compound exhibited fungicidal activity (i.e., a 99% reduction in viability) within 3 to 7 h at concentrations ranging from 0.06 to 1 microg/ml (0.25 to 4 times the MIC). Drug combination studies with MK-0991 plus amphotericin B found that this combination was not antagonistic against C. albicans, C. neoformans, or A. fumigatus in vitro. Studies with 0 to 50% pooled human or mouse serum established that fungal susceptibility to MK-0991 was not significantly influenced by the presence of human or mouse serum. Results from resistance induction studies suggested that the susceptibility of C. albicans was not altered by repeated exposure (40 passages) to MK-0991. Erythrocyte hemolysis studies with MK-0991 with washed and unwashed human or mouse erythrocytes indicated minimal hemolytic potential with this compound. These favorable results of preclinical studies support further studies with MK-0991 with humans.[4]
|
| Cell Assay |
Effect of coating the wells of a microtiter plate with caspofungin on C. albicans biofilm formation. A modified assay was used in which the wells of a microtiter plate were directly precoated with caspofungin in order to investigate the drug's ability to prevent biofilm formation. Briefly, 200-μl volumes of caspofungin at different concentrations in sterile PBS were added to selected wells of a microtiter plate and incubated overnight at 4°C. After incubation, excess caspofungin was aspirated and the plates were washed once in sterile PBS. C. albicans 3153A cells were washed in PBS and resuspended at a concentration of 106 cells per ml in RPMI 1640. The 96-well microtiter plates were then seeded with the suspension (100 μl per well) and incubated for 24 h at 37°C to allow biofilm formation. The contents of the wells were aspirated and washed three times in sterile PBS, and the extent of biofilm formation was assessed by the XTT reduction assay and by light microscopy. The inhibitory effect of caspofungin was expressed as the percentage of the optical density (OD) of caspofungin-treated wells compared to that of control (plastic) wells for the XTT assays. Statistical analysis was performed with Student's t test. P values of <0.05 were considered statistically significant. The analyses were performed by using Prism version 3.00 for Window.[3]
|
| Animal Protocol |
Animal/Disease Models: DBA/2N mice deficient in complement component 5 [1]
Doses: 1, 2, 4 and 8 mg/kg Route of Administration: intraperitoneal (ip) injection; one time/day for 7 days Experimental Results: diminished concentration of Candida load in the brain. Animal/Disease Models: Male C57BL/6 mice [2] Doses: 0.41, 1.2, 2.5, 4.1 and 41 μM Route of Administration: intraperitoneal (ip) injection; continued for 5 weeks Experimental Results: ERG waveform changed from 0.41 μM to 4.1 μM, no significant change . |
| References |
[1]. Flattery AM, et, al. Efficacy of caspofungin in a juvenile mouse model of central nervous system candidiasis. Antimicrob Agents Chemother. 2011 Jul;55(7):3491-7.
[2]. Mojumder DK, et, al. Evaluating retinal toxicity of intravitreal caspofungin in the mouse eye. Invest Ophthalmol Vis Sci. 2010 Nov;51(11):5796-803. [3]. Antimicrob Agents Chemother. 2002 Nov; 46(11): 3591–3596. [4]. Antimicrob Agents Chemother.1997 Nov;41(11):2326-32 |
| Additional Infomation |
Neonatal candidiasis is an increasingly common occurrence causing significant morbidity and mortality and a higher risk of dissemination to the central nervous system (CNS) than that seen with older patients. The current understanding of optimal antifungal therapy in this setting is limited. We have developed a model of disseminated candidiasis with CNS involvement in juvenile mice to assess the efficacy of the echinocandin caspofungin relative to amphotericin B (AmB). Juvenile mice were inoculated intravenously with 5.64 × 10(4) CFU of Candida albicans MY1055. Treatment with caspofungin at 1, 2, 4, and 8 mg/kg of body weight/day, AmB at 1 mg/kg/day, or a vehicle control (VC) was initiated 30 h after infection and continued for 7 days. Pharmacokinetic parameters for caspofungin were also determined. Culture and histology showed evidence of disseminated candidiasis with multifocal encephalitis at the start of antifungal therapy. Survival was 100% in all treated groups, while mortality was 100% in the VC by day 11 after infection. By day 5, all mice in the caspofungin treatment (four doses) groups showed reductions in kidney and brain burden relative to the VC, while AmB treatment reduced kidney burden but gave no reduction of brain fungal burden. Systemic levels of caspofungin were similar in infected and uninfected mice, while brain levels were higher in infected animals. In this juvenile mouse model, caspofungin demonstrated dose-dependent activity, equivalent to or better than that of AmB at 1 mg/kg, against disseminated candidiasis with CNS involvement.
References: Antimicrob Agents Chemother. 2011 Jul;55(7):3491-7. doi: 10.1128/AAC.01328-10. |
| Molecular Formula |
C52H88N10O15
|
|---|---|
| Molecular Weight |
1093.31
|
| Exact Mass |
1091.65
|
| Elemental Analysis |
C, 57.13; H, 8.11; N, 12.81; O, 21.95
|
| CAS # |
162808-62-0
|
| Related CAS # |
Caspofungin diacetate;179463-17-3;Caspofungin-d4;1131958-73-0; 162808-62-0
|
| PubChem CID |
16119814
|
| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
|
| Density |
1.36g/cm3
|
| Boiling Point |
1408.1ºC at 760mmHg
|
| Flash Point |
805.4ºC
|
| Vapour Pressure |
0mmHg at 25°C
|
| Index of Refraction |
1.623
|
| LogP |
0.76
|
| tPSA |
400.0
|
| SMILES |
CCC(CC(CCCCCCCCC(NC1CC(O)C(NC(C2C(O)CCN2C(C(NC(C(NC(C3CC(O)CN3C(C(NC1=O)C(O)C)=O)=O)C(O)C(O)C4=CC=C(O)C=C4)=O)C(O)CCN)=O)=O)NCCN)=O)C)C
|
| InChi Key |
JYIKNQVWKBUSNH-WVDDFWQHSA-N
|
| InChi Code |
InChI=1S/C52H88N10O15/c1-5-28(2)24-29(3)12-10-8-6-7-9-11-13-39(69)56-34-26-38(68)46(55-22-21-54)60-50(75)43-37(67)19-23-61(43)52(77)41(36(66)18-20-53)58-49(74)42(45(71)44(70)31-14-16-32(64)17-15-31)59-48(73)35-25-33(65)27-62(35)51(76)40(30(4)63)57-47(34)72/h14-17,28-30,33-38,40-46,55,63-68,70-71H,5-13,18-27,53-54H2,1-4H3,(H,56,69)(H,57,72)(H,58,74)(H,59,73)(H,60,75)/t28-,29+,30+,33+,34-,35-,36+,37-,38+,40-,41-,42-,43-,44-,45-,46-/m0/s1
|
| Chemical Name |
(10R,12S)-N-((2R,6S,9S,11R,12S,14aS,15S,20S,23S,25aS)-20-((R)-3-amino-1-hydroxypropyl)-12-((2-aminoethyl)amino)-23-((1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl)-2,11,15-trihydroxy-6-((R)-1-hydroxyethyl)-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2',1'-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl)-10,12-dimethyltetradecanamide
|
| Synonyms |
L 743872; MK0991; L743872; MK 0991; L-743872; MK-0991
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9147 mL | 4.5733 mL | 9.1465 mL | |
| 5 mM | 0.1829 mL | 0.9147 mL | 1.8293 mL | |
| 10 mM | 0.0915 mL | 0.4573 mL | 0.9147 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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