{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}benzamido)-1,4,7,13,16,22-hexaazatricyclo[22.3.0.0^{9,13}]heptacosan-6-yl]-1,2-dihydroxyethyl]-2-hydroxyphenyl}oxidanesulfonic acid

• ChemBase ID: 1012
• Molecular Formular: C56H71N9O23S
• Molecular Mass: 1270.27444
• Monoisotopic Mass: 1269.43835058
• SMILES: N12[C@H](C(=O)N[C@@H]([C@@H](C[C@@H](C(=O)N[C@H](C(=O)N3[C@H](C(=O)N[C@H](C(=O)N[C@H](C1=O)[C@@H](CC(=O)N)O)[C@@H]([C@H](c1cc(OS(=O)(=O)O)c(cc1)O)O)O)C[C@H](C3)O)[C@H](O)C)NC(=O)c1ccc(c3noc(c3)c3ccc(cc3)OCCCCC)cc1)O)O)[C@H]([C@H](C2)C)O
• Canonical SMILES: CCCCCOc1ccc(cc1)c1onc(c1)c1ccc(cc1)C(=O)N[C@H]1C[C@@H](O)[C@@H](O)NC(=O)[C@@H]2[C@@H](O)[C@H](CN2C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]2N(C(=O)[C@@H](NC1=O)[C@H](O)C)C[C@@H](C2)O)[C@@H]([C@H](c1ccc(c(c1)OS(=O)(=O)O)O)O)O)[C@@H](CC(=O)N)O)C
• 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
• InChIKey: PIEUQSKUWLMALL-YABMTYFHSA-N

NAMES AND DATABASE IDS

Names

• 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}benzamido)-1,4,7,13,16,22-hexaazatricyclo[22.3.0.0^{9,13}]heptacosan-6-yl]-1,2-dihydroxyethyl]-2-hydroxyphenyl}oxidanesulfonic acid; {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}benzamido)-1,4,7,13,16,22-hexaazatricyclo[22.3.0.0^9,^1^3]heptacosan-6-yl]-1,2-dihydroxyethyl]-2-hydroxyphenyl}oxidanesulfonic acid
• IUPAC Traditional 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}benzamido)-1,4,7,13,16,22-hexaazatricyclo[22.3.0.0^{9,13}]heptacosan-6-yl]-1,2-dihydroxyethyl]-2-hydroxyphenyl}oxidanesulfonic acid; micafungin
• Brand Name: Mycamine
• Synonyms: micafungin; FK-463; Micafungin

Database IDs

• CAS Number: 235114-32-6
• PubChem SID: 46508208; 160964475
• PubChem CID: 477468
• ATC CODE: J02AX05
• CHEMBL: 1201351
• Chemspider ID: 21106351
• DrugBank ID: DB01141
• KEGG ID: D02465
• Unique Ingredient Identifier: R10H71BSWG
• Wikipedia Title: Micafungin

CALCULATED PROPERTIES

JChem

• Acid pKa: -2.1882572
• H Acceptors: 22
• H Donor: 16
• LogD (pH = 5.5): -6.740862
• LogD (pH = 7.4): -6.7417994
• Log P: -6.3384485
• Molar Refractivity: 303.071 cm^3
• Polarizability: 121.588326 Å^3
• Polar Surface Area: 510.14 Å^2
• Rotatable Bonds: 18
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 0.67
• LOG S: -3.77
• Solubility (Water): 2.18e-01 g/l

PROPERTIES

Physical Property

• Solubility: Freely soluble as sodium salt (> 200mg/mL)
• Hydrophobicity(logP): -1.5

Pharmacology Properties

• Admin Routes: Intravenous
• Excretion: 40% feces, <15% urine
• Half Life: 11–17 hours
• Metabolism: Via catechol-O-methyltransferase pathway
• Protein Bound: 99.8%
• Legal Status: Rx-only
• Pregnancy Category: C
• US Licence: Micafungin
• EU Licence: Mycamine

DETAILS

DrugBank - DB01141

• Drug Groups: approved; 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.
• 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.
• Pharmacology: 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.
• 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
• Biotransformation: 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.
• Absorption: Not absorbed orally
• Half Life: 14-17 hours
• 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.
• Elimination: Fecal excretion is the major route of elimination (total radioactivity at 28 days was 71% of the administered dose).
• Distribution: * 0.39 ± 0.11 L/kg [adult patients with esophageal candidiasis]
• 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]
• References: Grover ND: Echinocandins: A ray of hope in antifungal drug therapy. Indian J Pharmacol. 2010 Feb;42(1):9-11. [Pubmed] ; Bormann AM, Morrison VA: Review of the pharmacology and clinical studies of micafungin. Drug Des Devel Ther. 2009 Dec 29;3:295-302. [Pubmed] ; 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] ; 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] ; Chandrasekar PH, Sobel JD: Micafungin: a new echinocandin. Clin Infect Dis. 2006 Apr 15;42(8):1171-8. Epub 2006 Mar 14. [Pubmed] ; 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] ; 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] ; 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] ; 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] ; 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: Wikipedia; RxList; Drugs.com

REFERENCES

• 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
• 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
• 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
• 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
• Grover ND: Echinocandins: A ray of hope in antifungal drug therapy. Indian J Pharmacol. 2010 Feb;42(1):9-11. Pubmed
• Bormann AM, Morrison VA: Review of the pharmacology and clinical studies of micafungin. Drug Des Devel Ther. 2009 Dec 29;3:295-302. Pubmed
• 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
• 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
• Chandrasekar PH, Sobel JD: Micafungin: a new echinocandin. Clin Infect Dis. 2006 Apr 15;42(8):1171-8. Epub 2006 Mar 14. Pubmed
• 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