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Anidulafungin (formerly also named as LY303366; Eraxis; Ecalta), a novel semisynthetic echinocandin derivative, which inhibits glucan synthase activity, used as an antifungal drug. Anidulafungin has been reported to inhibit systemic isolates of Candida species with the MIC90 values of 0.08μg/ml, 0.32μg/ml, 0.32μg/ml and 5.12μg/ml for C.albicans (n=99), C.glabrata(n=18), C.tropicalis(n=10), and C.parapsilosis (n=10), respectively. In addition, Anidulafungin has been found to be active against Aspergillus species(n=20) with the MIC90 values of ~0.02μg/ml. Apart from these, Anidulafungin has been revealed to inactively restrain with the MIC90 values of >10.24μg/ml and 16μg/ml, for C.neoformans and B.dermatitidis, respectively .
Physicochemical Properties
| Molecular Formula | C58H73N7O17 | |
| Molecular Weight | 1140.24 | |
| Exact Mass | 1139.506 | |
| Elemental Analysis | C, 61.09; H, 6.45; N, 8.60; O, 23.85 | |
| CAS # | 166663-25-8 | |
| Related CAS # |
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| PubChem CID | 166548 | |
| Appearance | White to off-white solid powder | |
| Density | 1.5±0.1 g/cm3 | |
| Boiling Point | 1477.0±65.0 °C at 760 mmHg | |
| Flash Point | 847.0±34.3 °C | |
| Vapour Pressure | 0.0±0.3 mmHg at 25°C | |
| Index of Refraction | 1.688 | |
| LogP | -3.86 | |
| Hydrogen Bond Donor Count | 14 | |
| Hydrogen Bond Acceptor Count | 17 | |
| Rotatable Bond Count | 14 | |
| Heavy Atom Count | 82 | |
| Complexity | 2150 | |
| Defined Atom Stereocenter Count | 15 | |
| SMILES | CCCCCOC1=CC=C(C=C1)C2=CC=C(C=C2)C3=CC=C(C=C3)C(=O)N[C@@H]4C(=O)N[C@H]([C@@H](C)O)C(=O)N5[C@@H](C[C@H](O)C5)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N6[C@H](C(=O)N[C@H](O)[C@H](O)C4)[C@@H](O)[C@@H](C)C6)[C@H](O)[C@@H](O)C7=CC=C(O)C=C7 |
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| InChi Key | JHVAMHSQVVQIOT-DJLNKZBGSA-N | |
| InChi Code | InChI=1S/C58H73N7O17/c1-5-6-7-24-82-40-22-18-35(19-23-40)33-10-8-32(9-11-33)34-12-14-37(15-13-34)51(74)59-41-26-43(70)54(77)63-56(79)47-48(71)29(2)27-65(47)58(81)45(31(4)67)61-55(78)46(50(73)49(72)36-16-20-38(68)21-17-36)62-53(76)42-25-39(69)28-64(42)57(80)44(30(3)66)60-52(41)75/h8-23,29-31,39,41-50,54,66-73,77H,5-7,24-28H2,1-4H3,(H,59,74)(H,60,75)(H,61,78)(H,62,76)(H,63,79)/t29-,30-,31-,39+,41+,42-,43+,44-,45-,46-,47-,48-,49-,50+,54+/m0/s1 | |
| Chemical Name | N-((2R,6S,9S,11R,12R,14aS,15S,16S,20S,23S,25aS)-23-((1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl)-2,11,12,15-tetrahydroxy-6,20-bis((R)-1-hydroxyethyl)-16-methyl-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2',1'-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl)-4''-(pentyloxy)-[1,1':4',1''-terphenyl]-4-carboxamide | |
| Synonyms | LY303366; LY-303366; LY 303366; Vechinocandin; trade name: Eraxis; Ecalta. | |
| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Antifungal | ||
| ln Vitro | Anidulafungin has been reported to inhibit systemic isolates of Candida species with the MIC90 values of 0.08μg/ml, 0.32μg/ml, 0.32μg/ml and 5.12μg/ml for C.albicans (n=99), C.glabrata(n=18), C.tropicalis(n=10), and C.parapsilosis (n=10), respectively. In addition, Anidulafungin has been found to be active against Aspergillus species(n=20) with the MIC90 values of ~0.02μg/ml. Apart from these, Anidulafungin has been revealed to inactively restrain with the MIC90 values of >10.24μg/ml and 16μg/ml, for C.neoformans and B.dermatitidis, respectively. | ||
| ln Vivo |
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| Enzyme Assay | Anidulafungin has been reported to inhibit systemic isolates of Candida species with the MIC90 values of 0.08μg/ml, 0.32μg/ml, 0.32μg/ml and 5.12μg/ml for C.albicans (n=99), C.glabrata(n=18), C.tropicalis(n=10), and C.parapsilosis (n=10), respectively. I | ||
| Cell Assay | Before being used, fresh stocks of CD101 (previously known as SP 3025, biafungin, and AF-025) are prepared in 100% DMSO. Additionally prepared in 100% DMSO are the comparator antifungals Anidulafungin (ANF), Caspofungin (CSF), and Amphotericin B (AMB).In compliance with CLSI guidelines, MIC assays are carried out using broth microdilution; however, test compounds are prepared at a 50× final assay concentration, and 100 μL assay mixture volumes are employed (2 μL added to 98 μL of broth containing cells at 0.5×103 to 2.5×103 CFU/mL). A representative data set is presented, and each MIC assay is run at least three times. MIC values obtained for WT C. krusei strain ATCC 6258 for AMB, CSF, and ANF are compared with previously published CLSI 24-h broth microdilution QC ranges to evaluate quality control (QC) throughout the study[2]. | ||
| Animal Protocol |
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Less than 1% of the administered radioactive dose was excreted in the urine. Anidulafungin is not hepatically metabolized. 30 to 50 L 1 L/h Metabolism / Metabolites Hepatic metabolism of anidulafungin has not been observed. Anidulafungin is not a clinically relevant substrate, inducer, or inhibitor of cytochrome P450 (CYP450) isoenzymes. Anidulafungin undergoes slow chemical degradation at physiologic temperature and pH to a ring-opened peptide that lacks antifungal activity. Hepatic metabolism of anidulafungin has not been observed. Anidulafungin is not a clinically relevant substrate, inducer, or inhibitor of cytochrome P450 (CYP450) isoenzymes. Anidulafungin undergoes slow chemical degradation at physiologic temperature and pH to a ring-opened peptide that lacks antifungal activity. Route of Elimination: Less than 1% of the administered radioactive dose was excreted in the urine. Anidulafungin is not hepatically metabolized. Half Life: 40-50 hours Biological Half-Life 40-50 hours |
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| Toxicity/Toxicokinetics |
Toxicity Summary Anidulafungin is a semi-synthetic echinocandin with antifungal activity. Anidulafungin inhibits glucan synthase, an enzyme present in fungal, but not mammalian cells. This results in inhibition of the formation of 1,3-β-D-glucan, an essential component of the fungal cell wall, ultimately leading to osmotic instability and cell death. Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Because of the low levels of anidulafungin in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. If anidulafungin is required by the mother, it is not a reason to discontinue breastfeeding. ◉ Effects in Breastfed Infants A postpartum woman was treated with intravenous anidulafungin 100 mg once daily for 14 days. She withheld breastfeeding until the second day after completing her 14-day course of therapy. Her milk had detectable anidulafungin levels until 32 hours after the last dose. No gastrointestinal or other adverse effects were seen in the infant up to 72 hours after the last dose of drug. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding 84% Toxicity Data During clinical trials a single 400 mg dose of anidulafungin was inadvertently administered as a loading dose. No clinical adverse events were reported. The maximum non-lethal dose of anidulafungin in rats was 50 mg/kg, a dose which is equivalent to 10 times the recommended daily dose for esophageal candidiasis (50mg/day). |
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| References |
[1]. In vitro activity of a new semisynthetic echinocandin, LY-303366, against systemic isolates of Candida species, Cryptococcus neoformans, Blastomyces dermatitidis, and Aspergillus species. Antimicrob Agents Chemother. 1997 Apr;41(4):863-5. [2]. Characterization of In Vitro Resistance Development to the Novel Echinocandin CD101 in Candida Species. Antimicrob Agents Chemother. 2016 Sep 23;60(10):6100-7. |
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| Additional Infomation |
Anidulafungin is a semisynthetic echinocandin anti-fungal drug. It is active against Aspergillus and Candida species and is used for the treatment of invasive candidiasis. It is an azamacrocycle, a heterodetic cyclic peptide, a semisynthetic derivative, an echinocandin and an antibiotic antifungal drug. Anidulafungin or Eraxis is an anti-fungal drug manufactured by Pfizer that gained approval by the Food and Drug Administration (FDA) in February 21, 2006; it was previously known as LY303366. There is preliminary evidence that it has a similar safety profile to caspofungin. Anidulafungin is an Echinocandin Antifungal. Anidulafungin has been reported in Streptomyces with data available. Anidulafungin is a cyclic lipopeptide echinocandin derivative with antifungal activity. Anidulafungin inhibits 1,3 beta-D-glucan synthase, an enzyme involved in fungal cell wall synthesis, resulting in cell lysis and death. This agent is active against Candida species and Aspergillus. (NCI04) Anidulafungin or Eraxis is an anti-fungal drug manufactured by Pfizer that gained approval by the Food and Drug Administration (FDA) in February 21, 2006; it was previously known as LY303366. There is preliminary evidence that it has a similar safety profile to caspofungin. Echinocandin antifungal agent that is used in the treatment of CANDIDEMIA and CANDIDIASIS. Drug Indication For use in the treatment of the following fungal infections: Candidemia and other forms of Candida infections (intra-abdominal abscess, and peritonitis), Aspergillus infections, and esophageal candidiasis. Also considered an alternative treatment for oropharyngeal canaidiasis. FDA Label Treatment of invasive candidiasis in adults and paediatric patients aged 1 month to < 18 years. Treatment of invasive candidiasis Mechanism of Action Anidulafungin is a semi-synthetic echinocandin with antifungal activity. Anidulafungin inhibits glucan synthase, an enzyme present in fungal, but not mammalian cells. This results in inhibition of the formation of 1,3-β-D-glucan, an essential component of the fungal cell wall, ultimately leading to osmotic instability and cell death. Pharmacodynamics Anidulafungin is a semi-synthetic lipopeptide synthesized from a fermentation product of Aspergillus nidulans. Anidulafungin is an echinocandin, a class of antifungal drugs that inhibits the synthesis of 1,3-β-D-glucan, an essential component of fungal cell walls. Anidulafungin is active in vitro against many Candida, as well as some Aspergillus. Like other echinocandins, anidulafungin is not active against Cryptococcus neoformans, Trichosporon, Fusarium, or zygomycetes. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL ( ~87.7 mM ) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.19 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: 10% DMSO+90% Corn Oil: ≥ 2.5 mg/mL (2.19 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8770 mL | 4.3850 mL | 8.7701 mL | |
| 5 mM | 0.1754 mL | 0.8770 mL | 1.7540 mL | |
| 10 mM | 0.0877 mL | 0.4385 mL | 0.8770 mL |