Natamycin - DrugBank

ID Pharmacology Interactions References Trials Economics Properties Spectra Taxonomy

Targets (1)

Targets (1)Biointeractions (1)

Identification

Name

Natamycin

Accession Number

DB00826 (APRD01136)

Type

Small Molecule

Groups

Approved

Description

Amphoteric macrolide antifungal antibiotic from Streptomyces natalensis or S. chattanoogensis. It is used for a variety of fungal infections, mainly topically. [PubChem]

Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Natamicina

Natamycin

Natamycine

Natamycinum

Pimaracin

Pimaricin

External IDs

A-5283 / Antibiotic A-5283 / CL 12,625 / CL 12625 / E 235 / E-235 / INS NO.235 / INS-235

Product Ingredients

Not Available

Approved Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Natacyn	Suspension / drops	50 mg/mL	Ophthalmic	Alcon, Inc.	1980-12-31	Not applicable	US

Approved Generic Prescription Products

Not Available

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Name	Company
Delvocid	Not Available
Fukricin	Sanbe
InfectoMyk	Infectopharm
N-Mycin	Aristopharma
Natadrops	Cipla
Natamet	Sun
Natamycyna	Unia
Natezhen	Alcon
Natoph	Ibn Sina
Natoptic	FDC
Optinat	Jayson
Pimafucin	Astellas
Pimafusin	Elder
Pimaricin	Senju Seiyaku

Brand mixtures

Not Available

Categories

UNII

8O0C852CPO

CAS number

7681-93-8

Weight

Average: 665.733
Monoisotopic: 665.304740577

Chemical Formula

C₃₃H₄₇NO₁₃

InChI Key

NCXMLFZGDNKEPB-FFPOYIOWSA-N

InChI

InChI=1S/C33H47NO13/c1-18-10-8-6-4-3-5-7-9-11-21(45-32-30(39)28(34)29(38)19(2)44-32)15-25-27(31(40)41)22(36)17-33(42,47-25)16-20(35)14-24-23(46-24)12-13-26(37)43-18/h3-9,11-13,18-25,27-30,32,35-36,38-39,42H,10,14-17,34H2,1-2H3,(H,40,41)/b4-3+,7-5+,8-6+,11-9+,13-12+/t18-,19-,20+,21+,22+,23-,24-,25+,27-,28+,29-,30+,32+,33-/m1/s1

IUPAC Name

(1R,3S,5R,7R,8E,12R,14E,16E,18E,20E,22R,24S,25R,26S)-22-{[(2R,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy}-1,3,26-trihydroxy-12-methyl-10-oxo-6,11,28-trioxatricyclo[22.3.1.0⁵,⁷]octacosa-8,14,16,18,20-pentaene-25-carboxylic acid

SMILES

[H][C@@]12C[[email protected]](O)C[C@]3(O)C[[email protected]](O)[C@@H](C(O)=O)[C@]([H])(C[C@@H](O[C@]4([H])O[[email protected]](C)[C@@H](O)[[email protected]](N)[C@@H]4O)\C=C\C=C\C=C\C=C\C[C@@H](C)OC(=O)\C=C\[C@@]1([H])O2)O3

Pharmacology

Indication

For the treatment of fungal blepharitis, conjunctivitis, and keratitis caused by susceptible organisms including Fusarium solani keratitis.

Structured Indications

Pharmacodynamics

Natamycin is an antifungal drug for topical ophthalmic administration. It is a tetraene polyene antibiotic derived from Streptomyces natalensis. It possesses in vitro activity against a variety of yeast and filamentous fungi, including Candida, Aspergillus, Cephalosporium, Fusarium and Penicillium. Although the activity against fungi is dose-related, natamycin is predominantly fungicidal. Natamycin is not effective in vitro against gram-positive or gram-negative bacteria. Topical administration appears to produce effective concentrations of natamycin within the corneal stroma but not in intraocular fluid.

Mechanism of action

LIke other polyene antibiotics, Natamycin inhibits fungal growth by binding to sterols. Specifically, Natamycin binds to ergosterol in the plasma membrane, preventing ergosterol-dependent fusion of vacuoles, as well as membrane fusion and fission. This differs from the mechanism of most other polyene antibiotics, which tend to work by altering fungal membrane permeability instead.

Target	Kind	Pharmacological action	Actions	Organism	UniProt ID
Ergosterol	Small molecule	yes	binder	Candida albicans	not applicable	details

Absorption

Systemic absorption should not be expected following topical administration, and as with other polyene antibiotics, absorption from the gastrointestinal tract is very poor.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Not Available

Half life

Not Available

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Various Fungus Species

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction	Drug group
Amlodipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Amlodipine.	Approved
Amphotericin B	The therapeutic efficacy of Amphotericin B can be decreased when used in combination with Natamycin.	Approved, Investigational
Amrinone	The risk or severity of adverse effects can be increased when Natamycin is combined with Amrinone.	Approved
Azelnidipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Azelnidipine.	Approved
Azimilide	The risk or severity of adverse effects can be increased when Natamycin is combined with Azimilide.	Investigational
Barnidipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Barnidipine.	Approved
BCG vaccine	The therapeutic efficacy of Bcg can be decreased when used in combination with Natamycin.	Investigational
Benidipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Benidipine.	Approved
Bepridil	The risk or severity of adverse effects can be increased when Natamycin is combined with Bepridil.	Approved, Withdrawn
Buspirone	The metabolism of Buspirone can be decreased when combined with Natamycin.	Approved, Investigational
Busulfan	The serum concentration of Busulfan can be increased when it is combined with Natamycin.	Approved, Investigational
Carboxyamidotriazole	The risk or severity of adverse effects can be increased when Natamycin is combined with Cai.	Investigational
Cilnidipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Cilnidipine.	Approved
Cinnarizine	The risk or severity of adverse effects can be increased when Natamycin is combined with Cinnarizine.	Approved
Cisapride	The serum concentration of Cisapride can be increased when it is combined with Natamycin.	Approved, Investigational, Withdrawn
Clevidipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Clevidipine.	Approved
Conivaptan	The metabolism of Conivaptan can be decreased when combined with Natamycin.	Approved, Investigational
Cyclosporine	The metabolism of Cyclosporine can be decreased when combined with Natamycin.	Approved, Investigational, Vet Approved
Darodipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Darodipine.	Experimental
Didanosine	Didanosine can cause a decrease in the absorption of Natamycin resulting in a reduced serum concentration and potentially a decrease in efficacy.	Approved
Diltiazem	The risk or severity of adverse effects can be increased when Natamycin is combined with Diltiazem.	Approved
Docetaxel	The metabolism of Docetaxel can be decreased when combined with Natamycin.	Approved, Investigational
Dofetilide	The metabolism of Dofetilide can be decreased when combined with Natamycin.	Approved
Efonidipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Efonidipine.	Approved
Eperisone	The risk or severity of adverse effects can be increased when Natamycin is combined with Eperisone.	Approved, Investigational
Etravirine	The serum concentration of Etravirine can be increased when it is combined with Natamycin.	Approved
Felodipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Felodipine.	Approved, Investigational
Fendiline	The risk or severity of adverse effects can be increased when Natamycin is combined with Fendiline.	Withdrawn
Flunarizine	The risk or severity of adverse effects can be increased when Natamycin is combined with Flunarizine.	Approved
Fosphenytoin	The serum concentration of Natamycin can be decreased when it is combined with Fosphenytoin.	Approved
Gabapentin	The risk or severity of adverse effects can be increased when Natamycin is combined with Gabapentin.	Approved, Investigational
Gallopamil	The risk or severity of adverse effects can be increased when Natamycin is combined with Gallopamil.	Investigational
Isradipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Isradipine.	Approved
Lacidipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Lacidipine.	Approved
Lamotrigine	The risk or severity of adverse effects can be increased when Natamycin is combined with Lamotrigine.	Approved, Investigational
Lercanidipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Lercanidipine.	Approved, Investigational
Losartan	The metabolism of Losartan can be decreased when combined with Natamycin.	Approved
Magnesium Sulfate	The risk or severity of adverse effects can be increased when Natamycin is combined with Magnesium Sulfate.	Approved, Vet Approved
Manidipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Manidipine.	Approved
Mibefradil	The risk or severity of adverse effects can be increased when Natamycin is combined with Mibefradil.	Withdrawn
Naftopidil	The risk or severity of adverse effects can be increased when Natamycin is combined with Naftopidil.	Investigational
Nicardipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Nicardipine.	Approved
Nifedipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Nifedipine.	Approved
Niguldipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Niguldipine.	Experimental
Niludipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Niludipine.	Experimental
Nilvadipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Nilvadipine.	Approved
Nimesulide	The risk or severity of adverse effects can be increased when Natamycin is combined with Nimesulide.	Approved, Withdrawn
Nimodipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Nimodipine.	Approved
Nisoldipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Nisoldipine.	Approved
Nitrendipine	The risk or severity of adverse effects can be increased when Natamycin is combined with Nitrendipine.	Approved
Perhexiline	The risk or severity of adverse effects can be increased when Natamycin is combined with Perhexiline.	Approved
Phenytoin	The serum concentration of Phenytoin can be increased when it is combined with Natamycin.	Approved, Vet Approved
Picosulfuric acid	The therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Natamycin.	Approved
Pimozide	Natamycin may increase the arrhythmogenic activities of Pimozide.	Approved
Pinaverium	The risk or severity of adverse effects can be increased when Natamycin is combined with Pinaverium.	Approved
Pregabalin	The risk or severity of adverse effects can be increased when Natamycin is combined with Pregabalin.	Approved, Illicit, Investigational
Prenylamine	The risk or severity of adverse effects can be increased when Natamycin is combined with Prenylamine.	Withdrawn
Progesterone	The therapeutic efficacy of Progesterone can be decreased when used in combination with Natamycin.	Approved, Vet Approved
Quinidine	The metabolism of Quinidine can be decreased when combined with Natamycin.	Approved
Ranolazine	The metabolism of Ranolazine can be decreased when combined with Natamycin.	Approved, Investigational
Rifabutin	The serum concentration of Rifabutin can be increased when it is combined with Natamycin.	Approved
Rifampicin	The serum concentration of Rifampicin can be increased when it is combined with Natamycin.	Approved
Rifapentine	The serum concentration of Rifapentine can be increased when it is combined with Natamycin.	Approved
Risedronate	The risk or severity of adverse effects can be increased when Natamycin is combined with Risedronate.	Approved, Investigational
Solifenacin	The metabolism of Solifenacin can be decreased when combined with Natamycin.	Approved
Sucralfate	Sucralfate can cause a decrease in the absorption of Natamycin resulting in a reduced serum concentration and potentially a decrease in efficacy.	Approved
Sunitinib	The metabolism of Sunitinib can be decreased when combined with Natamycin.	Approved, Investigational
Tacrolimus	The metabolism of Tacrolimus can be decreased when combined with Natamycin.	Approved, Investigational
Tolfenamic Acid	The risk or severity of adverse effects can be increased when Natamycin is combined with Tolfenamic Acid.	Approved
Tranilast	The risk or severity of adverse effects can be increased when Natamycin is combined with Tranilast.	Approved, Investigational
Verapamil	The risk or severity of adverse effects can be increased when Natamycin is combined with Verapamil.	Approved
Vinpocetine	The risk or severity of adverse effects can be increased when Natamycin is combined with Vinpocetine.	Investigational
Xylometazoline	The risk or severity of adverse effects can be increased when Natamycin is combined with Xylometazoline.	Approved
Ziconotide	The risk or severity of adverse effects can be increased when Natamycin is combined with Ziconotide.	Approved
Zolpidem	The serum concentration of Zolpidem can be increased when it is combined with Natamycin.	Approved

Food Interactions

Not Available

References

Synthesis Reference

Michael A. Eisenschink, Phillip T. Olson, "Fermentation process for producing natamycin." U.S. Patent US5231014, issued July, 1982.

US5231014

General References

Not Available

External Links

Resource	Link
KEGG Drug	D00884
KEGG Compound	C08073
ChemSpider	10468784
BindingDB	50370755
ChEMBL	CHEMBL1200656
Therapeutic Targets Database	DAP001331
PharmGKB	PA164744325
RxList	http://www.rxlist.com/cgi/generic2/natamycin.htm
Drugs.com	http://www.drugs.com/cdi/natamycin.html
Wikipedia	Natamycin

ATC Codes

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1, 2	Completed	Treatment	Fungal Keratitis	1
3	Completed	Treatment	Eye Infections, Fungal / Ulcerative keratitis	1
3	Enrolling by Invitation	Treatment	Fungal Keratitis / Ulcerative keratitis	1
3	Terminated	Treatment	Fungal Keratitis	1
Not Available	Unknown Status	Treatment	Mycotic Corneal Ulcer	1

Pharmacoeconomics

Manufacturers

Alcon laboratories inc

Packagers

Alcon Laboratories

Dosage forms

Form	Route	Strength
Suspension / drops	Ophthalmic	50 mg/mL

Prices

Unit description	Cost	Unit
Natacyn eye drops	14.16USD	ml

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	290 dec °C	PhysProp
water solubility	4100 mg/L (at 21 °C)	TOMLIN,C (1994)
logP	1.1	Not Available
logS	-3.21	ADME Research, USCD

Predicted Properties

Property	Value	Source
Water Solubility	0.278 mg/mL	ALOGPS
logP	-3.5	ALOGPS
logP	-1.7	ChemAxon
logS	-3.4	ALOGPS
pKa (Strongest Acidic)	3.58	ChemAxon
pKa (Strongest Basic)	9.11	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	13	ChemAxon
Hydrogen Donor Count	7	ChemAxon
Polar Surface Area	230.99 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	169.88 m³·mol^-1	ChemAxon
Polarizability	68.58 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	-	0.8512
Blood Brain Barrier	-	0.9789
Caco-2 permeable	-	0.6947
P-glycoprotein substrate	Substrate	0.5926
P-glycoprotein inhibitor I	Non-inhibitor	0.7063
P-glycoprotein inhibitor II	Non-inhibitor	0.9224
Renal organic cation transporter	Non-inhibitor	0.9629
CYP450 2C9 substrate	Non-substrate	0.7748
CYP450 2D6 substrate	Non-substrate	0.8576
CYP450 3A4 substrate	Non-substrate	0.5291
CYP450 1A2 substrate	Non-inhibitor	0.9046
CYP450 2C9 inhibitor	Non-inhibitor	0.9154
CYP450 2D6 inhibitor	Non-inhibitor	0.9231
CYP450 2C19 inhibitor	Non-inhibitor	0.9025
CYP450 3A4 inhibitor	Non-inhibitor	0.8632
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9632
Ames test	Non AMES toxic	0.6606
Carcinogenicity	Non-carcinogens	0.9448
Biodegradation	Not ready biodegradable	0.9718
Rat acute toxicity	2.4181 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.994
hERG inhibition (predictor II)	Non-inhibitor	0.9406

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum Type	Description	Splash Key
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	Not Available

Taxonomy

Description

This compound belongs to the class of organic compounds known as aminoglycosides. These are molecules or a portion of a molecule composed of amino-modified sugars.

Kingdom

Organic compounds

Super Class

Organic oxygen compounds

Class

Organooxygen compounds

Sub Class

Carbohydrates and carbohydrate conjugates

Direct Parent

Aminoglycosides

Alternative Parents

Macrolides and analogues / Hexoses / O-glycosyl compounds / Beta hydroxy acids and derivatives / Oxanes / Dicarboxylic acids and derivatives / Enoate esters / Amino acids / 1,2-aminoalcohols / Lactones

Substituents

Aminoglycoside core / Macrolide / Hexose monosaccharide / O-glycosyl compound / Glycosyl compound / Beta-hydroxy acid / Hydroxy acid / Monosaccharide / Oxane / Dicarboxylic acid or derivatives

Molecular Framework

Aliphatic heteropolycyclic compounds

External Descriptors

Not Available

Targets

1. Ergosterol

Kind: Small molecule
Organism: Candida albicans
Pharmacological action: yes
Actions: binder

References

te Welscher YM, Jones L, van Leeuwen MR, Dijksterhuis J, de Kruijff B, Eitzen G, Breukink E: Natamycin inhibits vacuole fusion at the priming phase via a specific interaction with ergosterol. Antimicrob Agents Chemother. 2010 Jun;54(6):2618-25. doi: 10.1128/AAC.01794-09. Epub 2010 Apr 12. [PubMed:20385867 ]
te Welscher YM, ten Napel HH, Balague MM, Souza CM, Riezman H, de Kruijff B, Breukink E: Natamycin blocks fungal growth by binding specifically to ergosterol without permeabilizing the membrane. J Biol Chem. 2008 Mar 7;283(10):6393-401. doi: 10.1074/jbc.M707821200. Epub 2007 Dec 29. [PubMed:18165687 ]

Drug created on June 13, 2005 07:24 / Updated on July 18, 2017 16:53

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Structure for DB00826 (Natamycin)

Targets

References