DrugBank: Caspofungin (DB00520)

targets (1) enzymes (1) transporters (5)

Identification

Name

Caspofungin

Accession Number

DB00520 (APRD00199)

Type

small molecule

Groups

approved

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Capsofungin
Caspofungin acetate

Brand names

Cancidas

Brand name mixtures

Not Available

Categories

Antifungals
Antifungal Agents

CAS number

179463-17-3

Weight

Average: 1093.3131
Monoisotopic: 1092.643062196

Chemical Formula

C₅₂H₈₈N₁₀O₁₅

InChI Key

InChIKey=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

Plain Text

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[22.3.0.0^{9,13}]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

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Echinocandins
Lactams

Substructures

Echinocandins
Hydroxy Compounds
Benzyl Alcohols and Derivatives
Phenols and Derivatives
Amino Ketones
Aliphatic and Aryl Amines
Pyrrolidines
Benzene and Derivatives
Carboxylic Acids and Derivatives
Aminals and Derivatives
Alcohols and Polyols
Heterocyclic compounds
Aromatic compounds
Carboxamides and Derivatives
Phenylpropylamines
Lactams
Tyrosols
Phenyl Esters

Pharmacology

Indication

For the treatment of esophageal candidiasis and invasive aspergillosis in patients who are refractory to or intolerant of other therapies.

Pharmacodynamics

Caspofungin 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 action

Caspofungin 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.

Absorption

92% tissue distribution within 36-48 hours after intravenous infusion

Volume of distribution

Not Available

Protein binding

97%

Metabolism

Metabolized slowly by hydrolysis and N-acetylation

Route of elimination

After 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 life

9-11 hours

Clearance

12 mL/min [After single IV administration]

Toxicity

Side effects include rash, swelling, and nausea (rare)

Affected organisms

Aspergillis, Candida and other fungi

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Merck and co inc

Packagers

Cardinal Health
Merck & Co.
Oso Biopharmaceuticals Manufacturing LLC

Dosage forms

Form	Route	Strength
Powder, for solution	Intravenous

Prices

Unit description	Cost	Unit
Cancidas iv 70 mg vial	421.06 USD	vial
Cancidas iv 50 mg vial	405.25 USD	vial

Patents

Country	Patent Number	Approved	Expires
United States	5952300	1997-09-28	2017-09-28
United States	5378804	1993-03-16	2013-03-16
Canada	2251928	2003-06-17	2017-04-15
Canada	2118757	2002-05-14	2014-03-10

Properties

State

solid

Melting point

Not Available

Experimental Properties

Property	Value	Source
logP	0	PhysProp

Predicted Properties

Property	Value	Source
water solubility	3.67e-01 g/l	ALOGPS
logP	0.17	ALOGPS
logP	-4.87	ChemAxon Molconvert
logS	-3.47	ALOGPS
pKa	11.29	ChemAxon Molconvert
hydrogen acceptor count	18	ChemAxon Molconvert
hydrogen donor count	16	ChemAxon Molconvert
polar surface area	412.03	ChemAxon Molconvert
rotatable bond count	23	ChemAxon Molconvert
refractivity	278.78	ChemAxon Molconvert
polarizability	117.52	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

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.
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
Morrison VA: Caspofungin: an overview. Expert Rev Anti Infect Ther. 2005 Oct;3(5):697-705. Pubmed
McCormack PL, Perry CM: Caspofungin: a review of its use in the treatment of fungal infections. Drugs. 2005;65(14):2049-68. 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

Resource	Link
PubChem Compound	2826718
PubChem Substance	46508288
ChemSpider	411774
ChEBI	474180
ChEMBL	474180
Therapeutic Targets Database	DAP000547
Drug Product Database	2244266
RxList	http://www.rxlist.com/cgi/generic/caspofungin.htm
Drugs.com	http://www.drugs.com/cdi/caspofungin.html
Wikipedia	http://en.wikipedia.org/wiki/Caspofungin

ATC Codes

J02AX04

AHFS Codes

08:14.16

PDB Entries

Not Available

FDA label

show (87.9 KB)

MSDS

Not Available

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 Gene: fksA SNPs: SNPJam Report References: 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 Morrison VA: Caspofungin: an overview. Expert Rev Anti Infect Ther. 2005 Oct;3(5):697-705. Pubmed McCormack PL, Perry CM: Caspofungin: a review of its use in the treatment of fungal infections. Drugs. 2005;65(14):2049-68. 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

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:

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
Morrison VA: Caspofungin: an overview. Expert Rev Anti Infect Ther. 2005 Oct;3(5):697-705. Pubmed
McCormack PL, Perry CM: Caspofungin: a review of its use in the treatment of fungal infections. Drugs. 2005;65(14):2049-68. 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

Enzymes
1. Cytochrome P450 3A4 Actions: inhibitor 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 xenobiotics. The enzyme also hydroxylates etoposide UniProt ID: P08684 Gene: CYP3A4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Enzymes

1. Cytochrome P450 3A4

Actions: inhibitor

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 xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out

Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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 Actions: inhibitor 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, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase UniProt ID: O15245 Gene: SLC22A1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 Actions: inhibitor Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells UniProt ID: P08183 Gene: ABCB1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 Actions: inhibitor UniProt ID: Q4U2R8 Gene: hROAT1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 Actions: inhibitor Mediates the Na(+)-independent transport 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. May play an important role in the clearance of bile acids and organic anions from the liver UniProt ID: Q9Y6L6 Gene: SLCO1B1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 Actions: substrate Mediates the Na(+)-independent transport of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP) UniProt ID: Q9NPD5 Gene: SLCO1B3 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Transporters

1. Solute carrier family 22 member 1

Actions: inhibitor

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, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase

UniProt ID: O15245 Link_out

Gene: SLC22A1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out

Gene: ABCB1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out

Gene: hROAT1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Actions: inhibitor

Mediates the Na(+)-independent transport 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. May play an important role in the clearance of bile acids and organic anions from the liver

UniProt ID: Q9Y6L6 Link_out

Gene: SLCO1B1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Actions: substrate

Mediates the Na(+)-independent transport of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP)

UniProt ID: Q9NPD5 Link_out

Gene: SLCO1B3 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Comments

Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:04

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.