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Identification
NameMicafungin
Accession NumberDB01141  (APRD01114)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Micafungin is an antifungal drug. It belongs to the antifungal class of compounds known as echinocandins and exerts its effect by inhibiting the synthesis of 1,3-beta-D-glucan, an integral component of the fungal cell wall.

Structure
Thumb
Synonyms
SynonymLanguageCode
MycamineNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
MycamineNot Available
Brand mixturesNot Available
Categories
CAS number235114-32-6
WeightAverage: 1270.274
Monoisotopic: 1269.438350313
Chemical FormulaC56H71N9O23S
InChI KeyPIEUQSKUWLMALL-YABMTYFHSA-N
InChI
InChI=1S/C56H71N9O23S/c1-4-5-6-17-86-32-14-11-28(12-15-32)39-21-33(63-87-39)27-7-9-29(10-8-27)49(75)58-34-20-38(70)52(78)62-54(80)45-46(72)25(2)23-65(45)56(82)43(37(69)22-41(57)71)60-53(79)44(48(74)47(73)30-13-16-36(68)40(18-30)88-89(83,84)85)61-51(77)35-19-31(67)24-64(35)55(81)42(26(3)66)59-50(34)76/h7-16,18,21,25-26,31,34-35,37-38,42-48,52,66-70,72-74,78H,4-6,17,19-20,22-24H2,1-3H3,(H2,57,71)(H,58,75)(H,59,76)(H,60,79)(H,61,77)(H,62,80)(H,83,84,85)/t25-,26+,31+,34-,35-,37+,38+,42-,43-,44-,45-,46-,47-,48-,52+/m0/s1
IUPAC Name
{5-[(1S,2S)-2-[(3S,6S,9S,11R,15S,18S,20R,21R,24S,25S,26S)-3-[(1R)-2-carbamoyl-1-hydroxyethyl]-11,20,21,25-tetrahydroxy-15-[(1R)-1-hydroxyethyl]-26-methyl-2,5,8,14,17,23-hexaoxo-18-[(4-{5-[4-(pentyloxy)phenyl]-1,2-oxazol-3-yl}benzene)amido]-1,4,7,13,16,22-hexaazatricyclo[22.3.0.0^{9,13}]heptacosan-6-yl]-1,2-dihydroxyethyl]-2-hydroxyphenyl}oxidanesulfonic acid
SMILES
CCCCCOC1=CC=C(C=C1)C1=CC(=NO1)C1=CC=C(C=C1)C(=O)N[C@H]1C[C@@H](O)[C@@H](O)NC(=O)[C@@H]2[C@@H](O)[C@@H](C)CN2C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC1=O)[C@@H](C)O)[C@H](O)[C@@H](O)C1=CC(OS(O)(=O)=O)=C(O)C=C1)[C@H](O)CC(N)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentCyclic Peptides
Alternative parentsMacrolactams; N-acyl-alpha Amino Acids and Derivatives; Tyrosols and Derivatives; Phenylsulfates; Benzamides; Phenol Ethers; Benzoyl Derivatives; Alkyl Aryl Ethers; Sulfuric Acid Monoesters; Tertiary Carboxylic Acid Amides; Pyrrolidines; Isoxazoles; Tertiary Amines; Secondary Alcohols; Primary Carboxylic Acid Amides; Secondary Carboxylic Acid Amides; 1,2-Diols; Enolates; Polyamines; Enols; Carboxylic Acids
Substituentsn-acyl-alpha amino acid or derivative; macrolactam; tyrosol derivative; phenylsulfate; benzamide; benzoyl; phenol ether; sulfuric acid monoester; phenol derivative; alkyl aryl ether; benzene; sulfate-ester; isoxazole; tertiary carboxylic acid amide; sulfuric acid derivative; azole; pyrrolidine; secondary alcohol; secondary carboxylic acid amide; 1,2-diol; carboxamide group; polyol; tertiary amine; primary carboxylic acid amide; enolate; carboxylic acid; ether; enol; polyamine; alcohol; organonitrogen compound; amine
Classification descriptionThis compound belongs to the cyclic peptides. These are compounds containing a cyclic moiety bearing a peptide backbone.
Pharmacology
IndicationFor use in the treatment of candidemia, acute disseminated candidiasis, and certain other invasive Candida infections, as well as esophageal candidiasis, and prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation. Micafungin is also used as an alternative for the treatment of oropharyngeal candidiases and has been used with some success as primary or salvage therapy, alone or in combination with other antifungals, for the treatment of invasive aspergillosis.
PharmacodynamicsFormerly known as FK463, micafungin is a semisynthetic lipopeptide synthesized from a fermentation product of Coleophoma empetri that works as an antifungal agent. It is a glucan synthesis inhibitor of the echinocandin structural class. The U.S. Food and Drug Administration approved micafungin in March 2005. Micafungin inhibits an enzyme essential for fungal cell-wall synthesis. Depending on its concentration, micafungin may be fungicidal against some Candida, but is usually fungistatic against Apergillus. Micafungin can be used concomitantly with a variety of other drugs, including the HIV protease inhibitor ritonavir and the transplant medications cyclosporine and tacrolimus.
Mechanism of actionMicafungin inhibits the synthesis of beta-1,3-D-glucan, an essential component of fungal cell walls which is not present in mammalian cells. It does this by inhibiting beta-1,3-D-glucan synthase.
AbsorptionNot absorbed orally
Volume of distribution
  • 0.39 ± 0.11 L/kg [adult patients with esophageal candidiasis]
Protein bindingHighly (>99%) protein bound in vitro, independent of plasma concentrations over the range of 10 to 100 µg/mL. The primary binding protein is albumin; however, micafungin, at therapeutically relevant concentrations, does not competitively displace bilirubin binding to albumin. Micafungin also binds to a lesser extent to a1-acid-glycoprotein.
Metabolism

Micafungin is metabolized to M-1 (catechol form) by arylsulfatase, with further metabolism to M-2 (methoxy form) by catechol-O-methyltransferase. M-5 is formed by hydroxylation at the side chain (w-1 position) of micafungin catalyzed by cytochrome P450 (CYP) isozymes. Even though micafungin is a substrate for and a weak inhibitor of CYP3A in vitro, hydroxylation by CYP3A is not a major pathway for micafungin metabolism in vivo.

Route of eliminationFecal excretion is the major route of elimination (total radioactivity at 28 days was 71% of the administered dose).
Half life14-17 hours
Clearance
  • 0.359 +/- 0.179 mL/min/kg [Adult Patients with IC with 100 mg]
  • 0.321 +/- 0.098 mL/min/kg [HIV- Positive Patients with EC with 50 mg]
  • 0.327 +/- 0.093 mL/min/kg [HIV- Positive Patients with EC with 100 mg]
  • 0.340 +/- 0.092 mL/min/kg [HIV- Positive Patients with EC with 150 mg]
  • 0.214 +/- 0.031 mL/min/kg [hematopoietic stem cell transplant recipients 3 mg/kg]
  • 0.204 +/- 0.036 mL/min/kg [hematopoietic stem cell transplant recipients 4 mg/kg]
  • 0.224 +/- 0.064 mL/min/kg [hematopoietic stem cell transplant recipients 6 mg/kg]
  • 0.223 +/- 0.081 mL/min/kg [hematopoietic stem cell transplant recipients 8 mg/kg]
ToxicityIntravenous LD50 in rats is 125mg/kg. In dogs it is >200mg/kg. No cases of overdosage have been reported. Repeated daily doses up to 8 mg/kg (maximum total dose of 896 mg) in adult patients have been administered in clinical trials with no reported dose-limiting toxicity. The minimum lethal dose is 125 mg/kg in rats, equivalent to 8.1 times the recommended human clinical dose for esophageal candidiasis based on body surface area comparisons.
Affected organisms
  • Aspergillis, Candida and other fungi
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.8383
Blood Brain Barrier - 0.8524
Caco-2 permeable - 0.6464
P-glycoprotein substrate Substrate 0.7906
P-glycoprotein inhibitor I Non-inhibitor 0.6752
P-glycoprotein inhibitor II Non-inhibitor 0.9279
Renal organic cation transporter Non-inhibitor 0.9428
CYP450 2C9 substrate Non-substrate 0.8485
CYP450 2D6 substrate Non-substrate 0.7911
CYP450 3A4 substrate Substrate 0.5853
CYP450 1A2 substrate Non-inhibitor 0.7414
CYP450 2C9 substrate Non-inhibitor 0.7017
CYP450 2D6 substrate Non-inhibitor 0.8251
CYP450 2C19 substrate Non-inhibitor 0.693
CYP450 3A4 substrate Inhibitor 0.5393
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7703
Ames test Non AMES toxic 0.563
Carcinogenicity Carcinogens 0.5763
Biodegradation Not ready biodegradable 0.9916
Rat acute toxicity 2.5651 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9686
hERG inhibition (predictor II) Inhibitor 0.716
Pharmacoeconomics
Manufacturers
  • Astellas pharma us inc
Packagers
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous drip100 mg
Injection, powder, lyophilized, for solutionIntravenous drip50 mg
Prices
Unit descriptionCostUnit
Mycamine 100 mg vial224.4USDvial
Mycamine 50 mg vial112.2USDvial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States67741042001-01-082021-01-08
United States53766341994-12-272011-12-27
Canada22020582007-11-062015-09-29
Canada20447462001-08-072011-06-17
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubilityFreely soluble as sodium salt (> 200mg/mL)Not Available
logP-1.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.218ALOGPS
logP0.67ALOGPS
logP-6.3ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)-2.2ChemAxon
pKa (Strongest Basic)-3.6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count22ChemAxon
Hydrogen Donor Count16ChemAxon
Polar Surface Area510.14 Å2ChemAxon
Rotatable Bond Count18ChemAxon
Refractivity303.07 m3·mol-1ChemAxon
Polarizability128.22 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Grover ND: Echinocandins: A ray of hope in antifungal drug therapy. Indian J Pharmacol. 2010 Feb;42(1):9-11. Pubmed
  2. Bormann AM, Morrison VA: Review of the pharmacology and clinical studies of micafungin. Drug Des Devel Ther. 2009 Dec 29;3:295-302. Pubmed
  3. Vehreschild JJ, Cornely OA: Micafungin sodium, the second of the echinocandin class of antifungals: theory and practice. Future Microbiol. 2006 Aug;1:161-70. Pubmed
  4. Groll AH, Stergiopoulou T, Roilides E, Walsh TJ: Micafungin: pharmacology, experimental therapeutics and clinical applications. Expert Opin Investig Drugs. 2005 Apr;14(4):489-509. Pubmed
  5. Chandrasekar PH, Sobel JD: Micafungin: a new echinocandin. Clin Infect Dis. 2006 Apr 15;42(8):1171-8. Epub 2006 Mar 14. Pubmed
  6. Wiederhold NP, Lewis JS 2nd: The echinocandin micafungin: a review of the pharmacology, spectrum of activity, clinical efficacy and safety. Expert Opin Pharmacother. 2007 Jun;8(8):1155-66. Pubmed
  7. Ikeda F, Tanaka S, Ohki H, Matsumoto S, Maki K, Katashima M, Barrett D, Aoki Y: Role of micafungin in the antifungal armamentarium. Curr Med Chem. 2007;14(11):1263-75. Pubmed
  8. Sucher AJ, Chahine EB, Balcer HE: Echinocandins: the newest class of antifungals. Ann Pharmacother. 2009 Oct;43(10):1647-57. Epub 2009 Sep 1. Pubmed
  9. 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
  10. 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
External Links
ResourceLink
KEGG DrugD02465
KEGG CompoundC15819
PubChem Compound477468
PubChem Substance46508208
ChemSpider2339421
ChEBI600520
ChEMBLCHEMBL457547
Therapeutic Targets DatabaseDAP000548
PharmGKBPA164781026
RxListhttp://www.rxlist.com/cgi/generic4/mycamine.htm
Drugs.comhttp://www.drugs.com/cdi/micafungin.html
WikipediaMicafungin
ATC CodesJ02AX05
AHFS Codes
  • 8:14.16
PDB EntriesNot Available
FDA labelshow(139 KB)
MSDSshow(84.3 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. 1,3-beta-glucan synthase component FKS1

Kind: protein

Organism: Aspergillus niger (strain CBS 513.88 / FGSC A1513)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
1,3-beta-glucan synthase component FKS1 A2QLK4 Details

References:

  1. Sucher AJ, Chahine EB, Balcer HE: Echinocandins: the newest class of antifungals. Ann Pharmacother. 2009 Oct;43(10):1647-57. Epub 2009 Sep 1. Pubmed
  2. 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. Epub 2009 May 7. Pubmed
  3. 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
  4. 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
  5. Jarvis B, Figgitt DP, Scott LJ: Micafungin. Drugs. 2004;64(9):969-82; discussion 983-4. Pubmed

Enzymes

1. Catechol O-methyltransferase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Catechol O-methyltransferase P21964 Details

References:

  1. Groll AH, Stergiopoulou T, Roilides E, Walsh TJ: Micafungin: pharmacology, experimental therapeutics and clinical applications. Expert Opin Investig Drugs. 2005 Apr;14(4):489-509. Pubmed
  2. Wiederhold NP, Lewis JS 2nd: The echinocandin micafungin: a review of the pharmacology, spectrum of activity, clinical efficacy and safety. Expert Opin Pharmacother. 2007 Jun;8(8):1155-66. Pubmed

2. Arylsulfatase A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Arylsulfatase A P15289 Details

References:

  1. Groll AH, Stergiopoulou T, Roilides E, Walsh TJ: Micafungin: pharmacology, experimental therapeutics and clinical applications. Expert Opin Investig Drugs. 2005 Apr;14(4):489-509. Pubmed
  2. Wiederhold NP, Lewis JS 2nd: The echinocandin micafungin: a review of the pharmacology, spectrum of activity, clinical efficacy and safety. Expert Opin Pharmacother. 2007 Jun;8(8):1155-66. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13