Antifungal
Anidulafungin (LY303366) targets fungal β-1,3-glucan synthase (MIC range = 0.03–1 μg/mL against Candida species; MIC > 16 μg/mL against Cryptococcus neoformans and Blastomyces dermatitidis; MIC = 0.5–4 μg/mL against Aspergillus species) [1]

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.

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Anidulafungin (LY303366) exhibited potent in vitro antifungal activity against Candida species: MIC₉₀ = 0.03 μg/mL for Candida albicans, 0.125 μg/mL for Candida glabrata, 0.25 μg/mL for Candida tropicalis, and 0.5 μg/mL for Candida parapsilosis (microdilution assay) [1]
Anidulafungin (LY303366) showed weak activity against Cryptococcus neoformans and Blastomyces dermatitidis with MIC > 16 μg/mL, failing to inhibit fungal growth at clinically relevant concentrations [1]
Anidulafungin (LY303366) inhibited Aspergillus species growth with MIC = 0.5 μg/mL for Aspergillus fumigatus, 1 μg/mL for Aspergillus flavus, and 4 μg/mL for Aspergillus niger [1]
No in vitro resistance development to Anidulafungin (LY303366) was reported in the specified literatures; resistance data were limited to CD101 (a different echinocandin) [2]
Anidulafungin (LY303366) showed no cytotoxicity to human fibroblasts at concentrations up to 64 μg/mL [1]

NA

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

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Fungal β-1,3-glucan synthase activity assay: Membrane fractions isolated from Candida albicans were incubated with Anidulafungin (LY303366) (0.001–10 μg/mL), UDP-glucose (substrate), and reaction buffer at 30°C for 2 hours; synthesized β-1,3-glucan was quantified by specific dye binding and spectrophotometry to assess enzyme inhibition [1]

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].

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Antifungal MIC assay: Clinical isolates of Candida spp., Cryptococcus neoformans, Blastomyces dermatitidis, and Aspergillus spp. were seeded in 96-well plates (1×10³ CFU/well) and treated with Anidulafungin (LY303366) (0.001–64 μg/mL) for 48 hours (yeasts) or 72 hours (molds); MIC was defined as the lowest concentration inhibiting visible fungal growth [1]
Cytotoxicity assay: Human fibroblasts were seeded in 96-well plates (5×10³ cells/well) and treated with Anidulafungin (LY303366) (0.1–64 μg/mL) for 72 hours; cell viability was assessed by MTT assay (absorbance at 570 nm) [1]

Absorption, Distribution and Excretion
Less than 1% of the administered radioactive dose is excreted in the urine. Anifenzin is not metabolized in the liver.
30 to 50 liters
1 liter/hour

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Metabolism/Metabolites
No hepatic metabolism of anifenzin has been observed. Anifenzin is not a clinically relevant substrate, inducer, or inhibitor of cytochrome P450 (CYP450) isoenzymes. Anifenzin undergoes slow chemical degradation at physiological temperature and pH to an open-ring peptide lacking antifungal activity.
No hepatic metabolism of anifenzin has been observed. Anifenzin is not a clinically relevant substrate, inducer, or inhibitor of cytochrome P450 (CYP450) isoenzymes. Anifenzin undergoes slow chemical degradation at physiological temperature and pH to produce an open-ring peptide that lacks antifungal activity.
Excretion Route: Less than 1% of the administered radioactive dose is excreted in the urine. Anifenzin is not metabolized in the liver.
Half-life: 40-50 hours

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Biological half-life 40-50 hours

Toxicity Summary
Anifenzin is a semi-synthetic echinocandin antifungal drug. Anifenzin inhibits glucan synthase, an enzyme present in fungal cells but not in mammalian cells. This leads to the inhibition of 1,3-β-D-glucan formation (an important component of the fungal cell wall), ultimately resulting in osmotic instability and cell death.

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Effects During Pregnancy and Lactation
◉ Use During Lactation
Because the amount of anifenzin in breast milk is very low, the amount ingested by the infant is minimal, and no adverse effects are expected on breastfed infants. If the mother needs to use anifenzin, this is not a reason to discontinue breastfeeding.
◉ Effects on Breastfed Infants
A postpartum woman received 14 days of intravenous anifenzin at a dose of 100 mg once daily. She began breastfeeding on the second day after completing the 14-day course. Anifenzin was still detectable in her breast milk 32 hours after the last dose. No gastrointestinal or other adverse reactions occurred in the infant within 72 hours of the last administration.
◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found.

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Protein binding rate 84%

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Toxicity data In clinical trials, a single 400 mg dose of anidulafungin was accidentally administered as a loading dose. No adverse clinical events were reported. The maximum non-lethal dose of anidulafungin in rats is 50 mg/kg, which is equivalent to 10 times the recommended daily dose (50 mg/day) for esophageal candidiasis.

[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.

Anidulafungin is a semi-synthetic echinocandin antifungal drug. It is effective against Aspergillus and Candida species and is used to treat invasive candidiasis. It is an aza-macrocyclic compound, heterocyclic peptide, semi-synthetic derivative, and echinocandin antibiotic. Anifenzin (trade name: Eraxis) is an antifungal drug manufactured by Pfizer and approved by the U.S. Food and Drug Administration (FDA) on February 21, 2006; its predecessor was LY303366. Preliminary evidence suggests that anifenzin has a similar safety profile to caspofungin. Anifenzin is an echinocandin antifungal drug. Anifenzin has been reported to be effective against Streptomyces, and relevant data are available. Anifenzin is a cyclic lipopeptide echinocandin derivative with antifungal activity. Anifenzin inhibits 1,3β-D-glucan synthase (an enzyme involved in fungal cell wall synthesis), leading to cell lysis and death. This drug is effective against Candida and Aspergillus fungi. (NCI04)
Anifenzin (trade name: Eraxis) is an antifungal drug manufactured by Pfizer, approved by the U.S. Food and Drug Administration (FDA) on February 21, 2006; its original name was LY303366. Preliminary evidence suggests its safety profile is similar to caspofungin.
Echinocandins are antifungal drugs used to treat candidemia and candidiasis.
Drug Indications
For the treatment of the following fungal infections: candidemia and other forms of Candida infection (abdominal abscess and peritonitis), Aspergillus infection, and esophageal candidiasis. It may also be used as an alternative therapy for oropharyngeal candidiasis.
FDA Label
For the treatment of invasive candidiasis in adults and children aged 1 month to 18 years.
Treatment of Invasive Candidiasis

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Mechanism of Action>
Anifenzin is a semi-synthetic echinocandin with antifungal activity. Anifenzin inhibits glucan synthase, an enzyme present in fungal cells but not in mammalian cells. This leads to the inhibition of 1,3-β-D-glucan formation (an important component of the fungal cell wall), ultimately resulting in osmotic instability and cell death.

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Pharmacodynamics>
Anifenzin is a semi-synthetic lipopeptide synthesized from the fermentation products of Aspergillus nidulans. Anifenzin belongs to the echinocandin class of antifungal drugs, which exert their effects by inhibiting the synthesis of 1,3-β-D-glucan (an important component of the fungal cell wall). Anifenzin is active in vitro against various Candida species and some Aspergillus species. Like other echinocandins, anifenin is ineffective against Cryptococcus neoformans, Trichosporium, Fusarium, or Zygomycetes.

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Anifenin (LY303366) is a semi-synthetic echinocandin antifungal drug[1]
Its antifungal mechanism involves selectively inhibiting fungal β-1,3-glucan synthase, blocking fungal cell wall synthesis, and causing cell lysis[1]
It has strong in vitro activity against Candida and Aspergillus species, but no significant activity against Cryptococcus neoformans or Blastomyces dermatitidis[1]
The cited literature did not report in vitro resistance to anifenin (LY303366); the resistance characteristic analysis mainly focused on CD101, which is another echinocandin drug with unique structure and pharmacological properties[2]

C58H73N7O17

1140.24

1139.506

C, 61.09; H, 6.45; N, 8.60; O, 23.85

166663-25-8

166548

White to off-white solid powder

1.5±0.1 g/cm3

1477.0±65.0 °C at 760 mmHg

847.0±34.3 °C

0.0±0.3 mmHg at 25°C

1.688

-3.86

14

17

14

82

2150

15

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

JHVAMHSQVVQIOT-DJLNKZBGSA-N

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

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

LY303366; LY-303366; LY 303366; Vechinocandin; trade name: Eraxis; Ecalta.

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)

DMSO : ~100 mg/mL ( ~87.7 mM )

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.

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Solubility in Formulation 2: 10% DMSO+90% Corn Oil: ≥ 2.5 mg/mL (2.19 mM)

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