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Identification
NameAnidulafungin
Accession NumberDB00362  (APRD01301)
TypeSmall Molecule
GroupsApproved, Investigational
Description

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. [Wikipedia]

Structure
Thumb
Synonyms
(4R,5R)-4,5-Dihydroxy-N²-[[4''-(pentyloxy)-p-terphenyl-4-yl]carbonyl]-L-ornithyl-L-threonyl-trans-4-hydroxy-L-prolyl-(S)-4-hydroxy-4(p-hydroxyphenyl)-L-threonyl-L-threonyl-(3S,4S)-3-hydroxy-4-methyl-L-proline cyclic (6->1)-peptide
Anidulafungin
Anidulafungina
Anidulafungine
Anidulafunginum
Eraxis
N-[(3S,6S,9S,11R,15S,18S,20R,21R,24S,25S,26S)-6-[(1S,2R)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-11,20,21,25-tetrahydroxy-3,15-bis[(1R)-1-hydroxyethyl]-26-methyl-2,5,8,14,17,23-hexaoxo-1,4,7,13,16,22-hexaazatricyclo[22.3.0.09,13]heptacosan-18-yl]- 4-{4-[4-(pentyloxy)phenyl]phenyl}benzamide
V-Echinocandin
External Identifiers
  • LY-307853
  • LY-329960
  • LY-333006
  • LY303366
  • VEC
  • VER-002
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Eraxispowder for solution100 mgintravenousPfizer Canada Inc2010-01-25Not applicableCanada
Eraxisinjection, powder, lyophilized, for solution100 mg/30mLintravenousRoerig2006-02-17Not applicableUs
Eraxisinjection, powder, lyophilized, for solution50 mg/15mLintravenousRoerig2006-02-17Not applicableUs
Eraxispowder for solution100 mgintravenousPfizer Canada Inc2008-01-252013-07-19Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
EcaltaPfizer
Brand mixturesNot Available
SaltsNot Available
Categories
UNII9HLM53094I
CAS number166663-25-8
WeightAverage: 1140.2369
Monoisotopic: 1139.506293945
Chemical FormulaC58H73N7O17
InChI KeyInChIKey=JHVAMHSQVVQIOT-MFAJLEFUSA-N
InChI
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
IUPAC Name
N-[(3S,6S,9S,11R,15S,18S,20R,21R,24S,25S,26S)-6-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-11,20,21,25-tetrahydroxy-3,15-bis[(1R)-1-hydroxyethyl]-26-methyl-2,5,8,14,17,23-hexaoxo-1,4,7,13,16,22-hexaazatricyclo[22.3.0.0⁹,¹³]heptacosan-18-yl]-4-{4-[4-(pentyloxy)phenyl]phenyl}benzamide
SMILES
[H][C@@]12C[C@@H](O)CN1C(=O)[C@@]([H])(NC(=O)[[email protected]](C[C@@H](O)[C@@H](O)NC(=O)[C@]1([H])[C@@H](O)[C@@H](C)CN1C(=O)[C@@]([H])(NC(=O)[C@@]([H])(NC2=O)[[email protected]](O)[C@@H](O)C1=CC=C(O)C=C1)[C@@H](C)O)NC(=O)C1=CC=C(C=C1)C1=CC=C(C=C1)C1=CC=C(OCCCCC)C=C1)[C@@H](C)O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as cyclic peptides. These are compounds containing a cyclic moiety bearing a peptide backbone.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentCyclic peptides
Alternative Parents
Substituents
  • Cyclic alpha peptide
  • Terphenyl
  • Para-terphenyl
  • N-acyl-alpha amino acid or derivatives
  • Macrolactam
  • Biphenyl
  • Benzoic acid or derivatives
  • Benzamide
  • Phenol ether
  • Benzoyl
  • Phenol
  • Alkyl aryl ether
  • Benzenoid
  • Monocyclic benzene moiety
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Polyol
  • Lactam
  • Carboxamide group
  • 1,2-diol
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Carboxylic acid amide
  • Alkanolamine
  • Hydrocarbon derivative
  • Aromatic alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor 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.
PharmacodynamicsAnidulafungin 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.
Mechanism of actionAnidulafungin 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.
Related Articles
AbsorptionNot Available
Volume of distribution
  • 30 to 50 L
Protein binding84%
Metabolism

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 eliminationLess than 1% of the administered radioactive dose was excreted in the urine. Anidulafungin is not hepatically metabolized.
Half life40-50 hours
Clearance
  • 1 L/h
ToxicityDuring 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).
Affected organisms
  • Candida albicans and other yeasts
  • Aspergillis, Candida and other fungi
  • Candida parapsilosis
  • Coolia tropicalis
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6513
Blood Brain Barrier-0.9833
Caco-2 permeable-0.7967
P-glycoprotein substrateSubstrate0.9066
P-glycoprotein inhibitor INon-inhibitor0.6298
P-glycoprotein inhibitor IIInhibitor0.6296
Renal organic cation transporterNon-inhibitor0.9085
CYP450 2C9 substrateNon-substrate0.7737
CYP450 2D6 substrateNon-substrate0.8428
CYP450 3A4 substrateSubstrate0.644
CYP450 1A2 substrateNon-inhibitor0.949
CYP450 2C9 inhibitorNon-inhibitor0.8978
CYP450 2D6 inhibitorNon-inhibitor0.8104
CYP450 2C19 inhibitorNon-inhibitor0.8827
CYP450 3A4 inhibitorNon-inhibitor0.8221
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8637
Ames testNon AMES toxic0.7638
CarcinogenicityNon-carcinogens0.8077
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7797 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9863
hERG inhibition (predictor II)Inhibitor0.6881
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Vicuron pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionintravenous100 mg/30mL
Injection, powder, lyophilized, for solutionintravenous50 mg/15mL
Powder for solutionintravenous100 mg
Prices
Unit descriptionCostUnit
Eraxis(water dil) 100 mg vial216.0USD vial
Eraxis(water dil) 50 mg vial108.0USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2091663 No2007-10-302013-03-15Canada
CA2362481 No2008-11-042020-03-02Canada
US5965525 No2000-02-172020-02-17Us
US6384013 No1995-03-192012-03-19Us
US6960564 No2001-04-122021-04-12Us
US7198796 No2002-06-132022-06-13Us
US7709444 No2001-04-122021-04-12Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityPractically insolubleNot Available
logP2.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0564 mg/mLALOGPS
logP1.87ALOGPS
logP-1.5ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)9.46ChemAxon
pKa (Strongest Basic)-3.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count17ChemAxon
Hydrogen Donor Count14ChemAxon
Polar Surface Area377.42 Å2ChemAxon
Rotatable Bond Count14ChemAxon
Refractivity292.29 m3·mol-1ChemAxon
Polarizability122.38 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Scott Jenkins, Gary Liversidge, Deborah Neville, “Nanoparticulate Anidulafungin Compositions and Methods for Making the Same.” U.S. Patent US20090238867, issued September 24, 2009.

US20090238867
General References
  1. Cappelletty D, Eiselstein-McKitrick K: The echinocandins. Pharmacotherapy. 2007 Mar;27(3):369-88. [PubMed:17316149 ]
  2. Vazquez JA: Anidulafungin: a new echinocandin with a novel profile. Clin Ther. 2005 Jun;27(6):657-73. [PubMed:16117974 ]
  3. Grover ND: Echinocandins: A ray of hope in antifungal drug therapy. Indian J Pharmacol. 2010 Feb;42(1):9-11. doi: 10.4103/0253-7613.62396. [PubMed:20606829 ]
  4. Vazquez JA: The safety of anidulafungin. Expert Opin Drug Saf. 2006 Nov;5(6):751-8. [PubMed:17044802 ]
  5. Menichetti F: Anidulafungin, a new echinocandin: effectiveness and tolerability. Drugs. 2009;69 Suppl 1:95-7. doi: 10.2165/11315570-000000000-00000. [PubMed:19877741 ]
  6. Vazquez JA, Sobel JD: Anidulafungin: a novel echinocandin. Clin Infect Dis. 2006 Jul 15;43(2):215-22. Epub 2006 Jun 9. [PubMed:16779750 ]
  7. Estes KE, Penzak SR, Calis KA, Walsh TJ: Pharmacology and antifungal properties of anidulafungin, a new echinocandin. Pharmacotherapy. 2009 Jan;29(1):17-30. doi: 10.1592/phco.29.1.17. [PubMed:19113794 ]
  8. Morace G, Borghi E, Iatta R, Montagna MT: Anidulafungin, a new echinocandin: in vitro activity. Drugs. 2009;69 Suppl 1:91-4. doi: 10.2165/11315560-000000000-00000. [PubMed:19877740 ]
External Links
ATC CodesJ02AX06
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (2.25 MB)
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Aspergillus niger (strain CBS 513.88 / FGSC A1513)
Pharmacological action
yes
Actions
inhibitor
General Function:
1,3-beta-d-glucan synthase activity
Specific Function:
Catalytic subunit of the 1,3-beta-glucan synthase. Synthesizes 1,3-beta-glucan, a major structural component of the cell wall. Involved in cell wall synthesis, maintenance and cell wall remodeling (By similarity).
Gene Name:
fksA
Uniprot ID:
A2QLK4
Molecular Weight:
216972.8 Da
References
  1. Sucher AJ, Chahine EB, Balcer HE: Echinocandins: the newest class of antifungals. Ann Pharmacother. 2009 Oct;43(10):1647-57. doi: 10.1345/aph.1M237. Epub 2009 Sep 1. [PubMed:19724014 ]
  2. Morris MI, Villmann M: Echinocandins in the management of invasive fungal infections, part 1. Am J Health Syst Pharm. 2006 Sep 15;63(18):1693-703. [PubMed:16960253 ]
  3. Morris MI, Villmann M: Echinocandins in the management of invasive fungal infections, Part 2. Am J Health Syst Pharm. 2006 Oct 1;63(19):1813-20. [PubMed:16990627 ]
  4. Ponton J: [The fungal cell wall and the mechanism of action of anidulafungin]. Rev Iberoam Micol. 2008 Jun;25(2):78-82. [PubMed:18473501 ]
  5. Quindos G, Eraso E, Javier Carrillo-Munoz A, Canton E, Peman J: [In vitro antifungal activity of micafungin]. Rev Iberoam Micol. 2009 Mar 31;26(1):35-41. doi: 10.1016/S1130-1406(09)70006-3. Epub 2009 May 7. [PubMed:19463275 ]
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Drug created on June 13, 2005 07:24 / Updated on June 26, 2016 01:52