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Identification
NameCaspofungin
Accession NumberDB00520  (APRD00199)
TypeSmall Molecule
GroupsApproved
Description

Caspofungin (brand name Cancidas worldwide) is an antifungal drug, the first of a new class termed the echinocandins from Merck & Co., Inc. It shows activity against infections with Aspergillus and Candida, and works by inhibiting β(1,3)-D-Glucan of the fungal cell wall. Caspofungin is administered intravenously.

Structure
Thumb
Synonyms
SynonymLanguageCode
(4R,5S)-5-((2-Aminoethyl)amino)-N(2)-(10,12-dimethyltetradecanoyl)-4-hydroxy-L-ornithyl-L-threonyl-trans-4-hydroxy-L-prolyl-(S)-4-hydroxy-4-(P-hydroxyphenyl)-L-threonyl-threo-3-hydroxy-L-ornithyl-trans-3-hydroxy-L-proline cyclic (6-1)-peptideNot AvailableNot Available
1-[(4R,5S)-5-[(2-Aminoethyl)amino]-N(2)-(10,12-dimethyl-1-oxotetradecyl)-4-hydroxy-L-ornithine]-5-[(3R)-3-hydroxy-L-ornithine]-pneumocandin b0Not AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cancidasinjection, powder, lyophilized, for solution5 mg/mLintravenousMerck Sharp & Dohme Corp.2001-01-26Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Cancidasinjection, powder, lyophilized, for solution7 mg/mLintravenousMerck Sharp & Dohme Corp.2001-01-26Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Cancidaspowder for solution50 mgintravenousMerck Canada IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Cancidaspowder for solution70 mgintravenousMerck Canada IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Caspofungin acetate
179463-17-3
Thumb
  • InChI Key: OGUJBRYAAJYXQP-LLXMLGLCSA-N
  • Monoisotopic Mass: 1212.68532094
  • Average Mass: 1213.417
DBSALT000020
Categories
CAS number162808-62-0
WeightAverage: 1093.3131
Monoisotopic: 1092.643062196
Chemical FormulaC52H88N10O15
InChI KeyJYIKNQVWKBUSNH-OGZDCFRISA-N
InChI
InChI=1S/C52H88N10O15/c1-5-28(2)24-29(3)12-10-8-6-7-9-11-13-39(69)56-34-26-38(68)46(55-22-21-54)60-50(75)43-37(67)19-23-61(43)52(77)41(36(66)18-20-53)58-49(74)42(45(71)44(70)31-14-16-32(64)17-15-31)59-48(73)35-25-33(65)27-62(35)51(76)40(30(4)63)57-47(34)72/h14-17,28-30,33-38,40-46,55,63-68,70-71H,5-13,18-27,53-54H2,1-4H3,(H,56,69)(H,57,72)(H,58,74)(H,59,73)(H,60,75)/t28?,29?,30-,33-,34+,35+,36-,37+,38-,40+,41+,42+,43+,44+,45+,46+/m1/s1
IUPAC Name
N-[(3S,6S,9S,11R,15S,18S,20R,21S,24S,25S)-3-[(1R)-3-amino-1-hydroxypropyl]-21-[(2-aminoethyl)amino]-6-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-11,20,25-trihydroxy-15-[(1R)-1-hydroxyethyl]-2,5,8,14,17,23-hexaoxo-1,4,7,13,16,22-hexaazatricyclo[22.3.0.0⁹,¹³]heptacosan-18-yl]-10,12-dimethyltetradecanamide
SMILES
CCC(C)CC(C)CCCCCCCCC(=O)N[C@H]1C[C@@H](O)[C@@H](NCCN)NC(=O)[C@@H]2[C@@H](O)CCN2C(=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=C(O)C=C1)[C@H](O)CCN
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
  • Phenol
  • Benzenoid
  • Monocyclic benzene moiety
  • Cyclic carboximidic acid
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • 1,3-aminoalcohol
  • Tertiary amine
  • Secondary alcohol
  • Polyol
  • Lactam
  • Carboxamide group
  • 1,2-diol
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Secondary amine
  • Secondary aliphatic amine
  • Carboximidic acid derivative
  • Carboximidic acid
  • Hydrocarbon derivative
  • Aromatic alcohol
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of esophageal candidiasis and invasive aspergillosis in patients who are refractory to or intolerant of other therapies.
PharmacodynamicsCaspofungin is an antifungal drug, and belongs to a new class termed the echinocandins. It is used to treat Aspergillus and Candida infection, and works by inhibiting cell wall synthesis. Antifungals in the echinocandin class inhibit the synthesis of glucan in the cell wall, probably via the enzyme 1,3-beta glucan synthase. There is a potential for resistance development to occur, however in vitro resistance development to Caspofungin by Aspergillus species has not been studied.
Mechanism of actionCaspofungin inhibits the synthesis of beta-(1,3)-D-glucan, an essential component of the cell wall of Aspergillus species and Candida species. beta-(1,3)-D-glucan is not present in mammalian cells. The primary target is beta-(1,3)-glucan synthase.
Absorption92% tissue distribution within 36-48 hours after intravenous infusion
Volume of distributionNot Available
Protein binding97%
Metabolism

Metabolized slowly by hydrolysis and N-acetylation

Route of eliminationAfter single intravenous administration of [3H] caspofungin acetate, excretion of caspofungin and its metabolites in humans was 35% of dose in feces and 41% of dose in urine.
Half life9-11 hours
Clearance
  • 12 mL/min [After single IV administration]
ToxicitySide effects include rash, swelling, and nausea (rare)
Affected organisms
  • Aspergillis, Candida and other fungi
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7566
Blood Brain Barrier-0.96
Caco-2 permeable-0.8091
P-glycoprotein substrateSubstrate0.8694
P-glycoprotein inhibitor INon-inhibitor0.9653
P-glycoprotein inhibitor IINon-inhibitor0.9174
Renal organic cation transporterNon-inhibitor0.9379
CYP450 2C9 substrateNon-substrate0.831
CYP450 2D6 substrateNon-substrate0.8166
CYP450 3A4 substrateNon-substrate0.51
CYP450 1A2 substrateNon-inhibitor0.9389
CYP450 2C9 substrateNon-inhibitor0.9161
CYP450 2D6 substrateNon-inhibitor0.8904
CYP450 2C19 substrateNon-inhibitor0.875
CYP450 3A4 substrateNon-inhibitor0.9682
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9781
Ames testNon AMES toxic0.7398
CarcinogenicityNon-carcinogens0.8315
BiodegradationNot ready biodegradable0.9683
Rat acute toxicity2.9344 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9637
hERG inhibition (predictor II)Non-inhibitor0.716
Pharmacoeconomics
Manufacturers
  • Merck and co inc
Packagers
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionintravenous5 mg/mL
Injection, powder, lyophilized, for solutionintravenous7 mg/mL
Powder for solutionintravenous50 mg
Powder for solutionintravenous70 mg
Prices
Unit descriptionCostUnit
Cancidas iv 70 mg vial421.06USD vial
Cancidas iv 50 mg vial405.25USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada21187572002-05-142014-03-10
Canada22519282003-06-172017-04-15
United States53788041993-03-162013-03-16
United States59523001997-09-282017-09-28
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP0Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.367 mg/mLALOGPS
logP0.17ALOGPS
logP-4.8ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)8.75ChemAxon
pKa (Strongest Basic)9.76ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count18ChemAxon
Hydrogen Donor Count16ChemAxon
Polar Surface Area412.03 Å2ChemAxon
Rotatable Bond Count23ChemAxon
Refractivity278.78 m3·mol-1ChemAxon
Polarizability117.52 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
References
Synthesis Reference

Johannes Ludescher, Ingolf Macher, Ole Storm, Stephan Bertel, “Process and Intermediates for the Synthesis of Caspofungin.” U.S. Patent US20080319162, issued December 25, 2008.

US20080319162
General Reference
  1. Letscher-Bru, Valérie, and Raoul Herbrecht. 2003. Caspofungin: the first representative of a new antifungal class. Journal of Antimicrobial Chemotherapy 51, no. 3 (March 1): 513 -521. doi:10.1093/jac/dkg117.
  2. 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
  3. Morrison VA: Caspofungin: an overview. Expert Rev Anti Infect Ther. 2005 Oct;3(5):697-705. Pubmed
  4. McCormack PL, Perry CM: Caspofungin: a review of its use in the treatment of fungal infections. Drugs. 2005;65(14):2049-68. Pubmed
  5. 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
  6. 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
ATC CodesJ02AX04
AHFS Codes
  • 08:14.16
PDB EntriesNot Available
FDA labelDownload (87.9 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
CarbamazepineInducers of Drug Clearance may decrease the serum concentration of Caspofungin.
NevirapineInducers of Drug Clearance may decrease the serum concentration of Caspofungin.
PhenytoinInducers of Drug Clearance may decrease the serum concentration of Caspofungin.
RifampicinRifampin may decrease the serum concentration of Caspofungin.
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. Morrison VA: Caspofungin: an overview. Expert Rev Anti Infect Ther. 2005 Oct;3(5):697-705. Pubmed
  3. McCormack PL, Perry CM: Caspofungin: a review of its use in the treatment of fungal infections. Drugs. 2005;65(14):2049-68. Pubmed
  4. 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
  5. 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

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters

1. Solute carrier family 22 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 1 O15245 Details

References:

  1. Sandhu P, Lee W, Xu X, Leake BF, Yamazaki M, Stone JA, Lin JH, Pearson PG, Kim RB: Hepatic uptake of the novel antifungal agent caspofungin. Drug Metab Dispos. 2005 May;33(5):676-82. Epub 2005 Feb 16. Pubmed

2. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Sandhu P, Lee W, Xu X, Leake BF, Yamazaki M, Stone JA, Lin JH, Pearson PG, Kim RB: Hepatic uptake of the novel antifungal agent caspofungin. Drug Metab Dispos. 2005 May;33(5):676-82. Epub 2005 Feb 16. Pubmed

3. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Sandhu P, Lee W, Xu X, Leake BF, Yamazaki M, Stone JA, Lin JH, Pearson PG, Kim RB: Hepatic uptake of the novel antifungal agent caspofungin. Drug Metab Dispos. 2005 May;33(5):676-82. Epub 2005 Feb 16. Pubmed

4. Solute carrier organic anion transporter family member 1B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1B1 Q9Y6L6 Details

References:

  1. Sandhu P, Lee W, Xu X, Leake BF, Yamazaki M, Stone JA, Lin JH, Pearson PG, Kim RB: Hepatic uptake of the novel antifungal agent caspofungin. Drug Metab Dispos. 2005 May;33(5):676-82. Epub 2005 Feb 16. Pubmed

5. Solute carrier organic anion transporter family member 1B3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1B3 Q9NPD5 Details

References:

  1. Sandhu P, Lee W, Xu X, Leake BF, Yamazaki M, Stone JA, Lin JH, Pearson PG, Kim RB: Hepatic uptake of the novel antifungal agent caspofungin. Drug Metab Dispos. 2005 May;33(5):676-82. Epub 2005 Feb 16. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11