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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
(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)-peptide
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 b0
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cancidasinjection, powder, lyophilized, for solution5 mg/mLintravenousMerck Sharp & Dohme Corp.2001-01-26Not applicableUs
Cancidaspowder for solution70 mgintravenousMerck Canada Inc2001-10-23Not applicableCanada
Cancidaspowder for solution50 mgintravenousMerck Canada Inc2001-08-23Not applicableCanada
Cancidasinjection, powder, lyophilized, for solution7 mg/mLintravenousMerck Sharp & Dohme Corp.2001-01-26Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not 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
UNIIF0XDI6ZL63
CAS number162808-62-0
WeightAverage: 1093.3131
Monoisotopic: 1092.643062196
Chemical FormulaC52H88N10O15
InChI KeyInChIKey=JYIKNQVWKBUSNH-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[[email protected]]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)[[email protected]](O)[C@@H](O)C1=CC=C(O)C=C1)[[email protected]](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.
Related Articles
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 inhibitorNon-inhibitor0.9161
CYP450 2D6 inhibitorNon-inhibitor0.8904
CYP450 2C19 inhibitorNon-inhibitor0.875
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
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
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2118757 No2002-05-142014-03-10Canada
CA2251928 No2003-06-172017-04-15Canada
US5378804 No1993-03-162013-03-16Us
US5514650 Yes1995-07-262015-07-26Us
US5952300 Yes1997-09-282017-09-28Us
US6136783 Yes1997-09-282017-09-28Us
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
SpectraNot Available
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 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. Morrison VA: Caspofungin: an overview. Expert Rev Anti Infect Ther. 2005 Oct;3(5):697-705. [PubMed:16207161 ]
  3. McCormack PL, Perry CM: Caspofungin: a review of its use in the treatment of fungal infections. Drugs. 2005;65(14):2049-68. [PubMed:16162025 ]
  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:16960253 ]
  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:16990627 ]
External Links
ATC CodesJ02AX04
AHFS Codes
  • 08:14.16
PDB EntriesNot Available
FDA labelDownload (87.9 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
CarbamazepineThe serum concentration of Caspofungin can be decreased when it is combined with Carbamazepine.
CyclosporineThe risk or severity of adverse effects can be increased when Cyclosporine is combined with Caspofungin.
DexamethasoneThe serum concentration of Caspofungin can be decreased when it is combined with Dexamethasone.
EfavirenzThe serum concentration of Caspofungin can be decreased when it is combined with Efavirenz.
NevirapineThe serum concentration of Caspofungin can be decreased when it is combined with Nevirapine.
PhenytoinThe serum concentration of Caspofungin can be decreased when it is combined with Phenytoin.
RifampicinThe serum concentration of Caspofungin can be decreased when it is combined with Rifampicin.
TacrolimusThe serum concentration of Tacrolimus can be decreased when it is combined with Caspofungin.
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. Morrison VA: Caspofungin: an overview. Expert Rev Anti Infect Ther. 2005 Oct;3(5):697-705. [PubMed:16207161 ]
  3. McCormack PL, Perry CM: Caspofungin: a review of its use in the treatment of fungal infections. Drugs. 2005;65(14):2049-68. [PubMed:16162025 ]
  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:16960253 ]
  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:16990627 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Secondary active organic cation transmembrane transporter activity
Specific Function:
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine...
Gene Name:
SLC22A1
Uniprot ID:
O15245
Molecular Weight:
61153.345 Da
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:15716364 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
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:15716364 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-in...
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
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:15716364 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular Weight:
76447.99 Da
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:15716364 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP). Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B3
Uniprot ID:
Q9NPD5
Molecular Weight:
77402.175 Da
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:15716364 ]
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Drug created on June 13, 2005 07:24 / Updated on July 24, 2016 03:07