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Identification
Name Micafungin
Accession Number DB01141 (APRD01114)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
FK-463
Salts Not Available
Brand names
Name Company
Mycamine
Brand mixtures Not Available
Categories
  • Antifungals
  • Antifungal Agents
CAS number 235114-32-6
Weight Average: 1270.274
Monoisotopic: 1269.438350313
Chemical Formula C56H71N9O23S
InChI Key InChIKey=PIEUQSKUWLMALL-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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Echinocandins
  • Polypeptides
  • Lactams
Substructures
  • Echinocandins
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Phenols and Derivatives
  • Amino Ketones
  • Sulfuric Acids and Derivatives
  • Sulfonyls
  • Pyrrolidines
  • Ethers
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Sulfate Esters
  • Aminals and Derivatives
  • Isoxazoles
  • Carboxylic Acids and Derivatives
  • Carbamates and Derivatives
  • Catechols
  • Alcohols and Polyols
  • Polypeptides
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • Oxazoles
  • Lactams
  • Imines
  • Benzoyl Derivatives
  • Tyrosols
  • Phenyl Esters
  • Benzamides
Pharmacology
Indication For 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.
Pharmacodynamics Formerly 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 action Micafungin 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.
Absorption Not absorbed orally
Volume of distribution
  • 0.39 ± 0.11 L/kg [adult patients with esophageal candidiasis]
Protein binding Highly (>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 elimination Fecal excretion is the major route of elimination (total radioactivity at 28 days was 71% of the administered dose).
Half life 14-17 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]
Toxicity Intravenous 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
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Astellas pharma us inc
Packagers
Dosage forms
Form Route Strength
Injection, powder, lyophilized, for solution Intravenous drip 100 mg
Injection, powder, lyophilized, for solution Intravenous drip 50 mg
Prices
Unit description Cost Unit
Mycamine 100 mg vial 224.4 USD vial
Mycamine 50 mg vial 112.2 USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6774104 2001-01-08 2021-01-08
United States 5376634 1994-12-27 2011-12-27
Canada 2202058 2007-11-06 2015-09-29
Canada 2044746 2001-08-07 2011-06-17
Properties
State solid
Experimental Properties
Property Value Source
water solubility Freely soluble as sodium salt (> 200mg/mL) Not Available
logP -1.5 Not Available
Predicted Properties
Property Value Source
water solubility 2.18e-01 g/l ALOGPS
logP 0.67 ALOGPS
logP -6.3 ChemAxon
logS -3.8 ALOGPS
pKa (strongest acidic) -2.2 ChemAxon
pKa (strongest basic) -3.6 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 22 ChemAxon
hydrogen donor count 16 ChemAxon
polar surface area 510.14 ChemAxon
rotatable bond count 18 ChemAxon
refractivity 303.07 ChemAxon
polarizability 128.22 ChemAxon
References
Synthesis Reference Not 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
Resource Link
KEGG Drug D02465 Link_out
KEGG Compound C15819 Link_out
PubChem Compound 477468 Link_out
PubChem Substance 46508208 Link_out
ChemSpider 2339421 Link_out
ChEBI 600520 Link_out
ChEMBL 600520 Link_out
Therapeutic Targets Database DAP000548 Link_out
PharmGKB PA164781026 Link_out
RxList http://www.rxlist.com/cgi/generic4/mycamine.htm Link_out
Drugs.com http://www.drugs.com/cdi/micafungin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Micafungin Link_out
ATC Codes
  • J02AX05
AHFS Codes
  • 8:14.16
PDB Entries Not Available
FDA label show (139 KB)
MSDS show (84.3 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

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

Pharmacological action: yes
Actions: inhibitor
UniProt ID: A2QLK4 Link_out
Gene: fksA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol

UniProt ID: P21964 Link_out
Gene: COMT Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

Hydrolyzes cerebroside sulfate

UniProt ID: P15289 Link_out
Gene: ARSA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19