166663-25-8 Usage
Description
Anidulafungin, a semi-synthetic derivative of echinocandin B, has been developed
and launched as an intravenous treatment for serious fungal infections,
such as candidemia, Candida-derived peritonitis, intra-abdominal abscesses, and
esophageal candidiasis. As a non-competitive inhibitor of 1,3-b-D-glucan synthase,
which is responsible for the formation of glucan polymers, anidulafungin
interferes with the cell wall synthesis of most pathogenic fungi. This mode of
action is characteristic of the echinocandin class of antifungals. While the first
member of this class, cilofungin, was withdrawn due to toxicity associated with
the formulation vehicle, anidulafungin follows the successful introduction
of caspofungin and micafungin.
Compared to the other echinocandins,
anidulafungin appears to be more potent (MIC90 ofr0.25 mg/mL for C.albicans,
0.5 mg/mL for C.glabrata, 1 mg/mL for C. krusel and C.tropicalis, 2mg/mL for
C.lusitaniae, and 2 mg/mL for Aspergillus spp) and is devoid of significant drug
interactions since it is neither an inhibitor nor substrate of the cytochrome P450
isoenzymes. The emergence of the echinocandins circumvents the concern
regarding the rising resistance to the azole and amphotericin B antifungals; no
cross-resistance is expected because the echinocandins work at the cell wall
rather than the cell membrane.
Uses
Different sources of media describe the Uses of 166663-25-8 differently. You can refer to the following data:
1. Anidulafungin is a semi-synthetic cyclic lipopeptide belonging to the echinocandin class that was reported in 1995 and commercially developed by Eli Lilly. Anidulafungin inhibits the synthesis of β-(1,3)-D-glucan, an essential component of the cell wall of susceptible fungi and is extensively referenced in the literature with over 400 citations.
2. nucleoside reverse transcriptase inhibitor (NRTI) for HIV treatment in adults
Definition
ChEBI: A semisynthetic echinocandin anti-fungal drug. It is active against Aspergillus and Candida species and is used for the treatment of invasive candidiasis.
Brand name
Eraxis (Vicuron).
Antimicrobial activity
It is active against Aspergillus spp., Candida spp. and the cyst
stage of Pneumocystis jirovecii. Resistance has not yet been
reported.
Pharmaceutical Applications
A semisynthetic lipopeptide derived from a fermentation
product of Aspergillus nidulans. Formulated for intravenous
infusion.
Pharmacokinetics
Cmax 100 mg 1-h infusion: c. 9 mg/L end infusion
Plasma half-life: 18–27 h
Volume of distribution: 0.6 L/kg
Plasma protein binding: 84%
Blood concentrations increase in proportion to dosage. The
steady state is achieved on the first day after a loading dose
(twice the daily maintenance dose).
Distribution
Levels in the CSF are negligible.
Metabolism and excretion
Unlike caspofungin and micafungin, anidulafungin is not metabolized by the liver, but undergoes slow non-enzymatic degradation in the blood to a peptide breakdown product which is enzymatically degraded and excreted in the feces and bile. About 30% of a dose is eliminated in the feces, of which less than 10% is unchanged drug. Less than 1% of a dose is excreted in the urine. No dosage adjustment is required in patients with hepatic or renal impairment. Anidulafungin is not cleared by hemodialysis.
Clinical Use
Candidemia and certain invasive forms of candidosis
Esophageal candidosis
Side effects
Occasional histamine-mediated infusion-related reactions,
injection site reactions and transient abnormalities of liver
enzymes have been reported.
Drug interactions
Potentially hazardous interactions with other drugs
None known
Metabolism
Hepatic metabolism of anidulafungin has not been
observed. Anidulafungin is not a clinically relevant
substrate, inducer, or inhibitor of cytochrome P450
isoenzymes.
Anidulafungin undergoes slow chemical degradation at
physiologic temperature and pH to a ring-opened peptide
that lacks antifungal activity. The ring-opened product
is subsequently converted to peptidic degradants and
eliminated mainly through biliary excretion.
In a single-dose clinical study, radiolabelled
[14C]-anidulafungin (~88 mg) was administered to
healthy subjects. Approximately 30% of the administered
radioactive dose was eliminated in the faeces over 9 days,
of which less than 10% was intact drug. Less than 1%
of the administered radioactive dose was excreted in the
urine, indicating negligible renal clearance.
references
[1] zhanel gg1, karlowsky ja, harding ga, balko tv, zelenitsky sa, friesen m, kabani a, turik m, hoban dj. 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.
Check Digit Verification of cas no
The CAS Registry Mumber 166663-25-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,6,6,6,6 and 3 respectively; the second part has 2 digits, 2 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 166663-25:
(8*1)+(7*6)+(6*6)+(5*6)+(4*6)+(3*3)+(2*2)+(1*5)=158
158 % 10 = 8
So 166663-25-8 is a valid CAS Registry Number.
InChI:InChI=1/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
166663-25-8Relevant articles and documents
Commercialization and late-stage development of a semisynthetic antifungal API: Anidulafungin/D-fructose (eraxis)
Norris, Timothy,VanAlsten, John,Hubbs, Stephen,Ewing, Marcus,Cai, Weiling,Jorgensen, Matthew L.,Bordner, Jon,Jensen, Grace O.
, p. 447 - 455 (2008)
Many years ago anidulafungin 1 was identified as a potentially useful medicine for the treatment of fungal infections. Its chemical and physical properties as a relatively high molecular weight semisynthetic derived from echinocandin B proved to be a significant hurdle to its final presentation as a useful medicine. It has recently been approved as an intravenous treatment for invasive candidaisis, an increasingly common health hazard that is potentially life-threatening. The development and commercialization of this API, which is presented as a molecular mixture of anidulafungin and D-fructose is described. This includes, single crystal X-ray structures of the starting materials, the echinocandin B cyclic-peptide nucleus (ECBN · HCI) and the active ester 1-({[4 - (pentyloxy)-1,1 :4,1-terphenyl-4-yl]carbonyl}oxy)-1H-1,2,3- benzotriazole (TOBt). Details of the structure and properties of starting materials, scale-up chemistry and unusual crystallization phenomena associated with the API formation are discussed.
