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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyNatamycin
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
Structure for DB00826 (Natamycin)
- 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
- 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 
- International/Other Brands
- Delvocid / 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)
- Categories
- Alimentary Tract and Metabolism
- Anti-Bacterial Agents
- Anti-Infective Agents
- Anti-Infective Agents, Local
- Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents
- Antifungal Agents
- Antifungals for Dermatological Use
- Antifungals for Topical Use
- Antiinfectives and Antiseptics for Local Oral Treatment
- Dermatologicals
- Genito Urinary System and Sex Hormones
- Gynecological Antiinfectives and Antiseptics
- Intestinal Antiinfectives
- Lactones
- Macrolides
- Ophthalmologicals
- Polyene Antifungal
- Polyene Antimicrobial
- Polyketides
- Sensory Organs
- Stomatological Preparations
- 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[C@H](O)C[C@]3(O)C[C@H](O)[C@@H](C(O)=O)[C@]([H])(C[C@@H](O[C@]4([H])O[C@H](C)[C@@H](O)[C@H](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.
- Associated Conditions
- 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 Actions Organism AErgosterol binderCandida albicans - 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 Agmatine The therapeutic efficacy of Natamycin can be increased when used in combination with Agmatine. Experimental, Investigational Amiodarone The therapeutic efficacy of Natamycin can be increased when used in combination with Amiodarone. Approved, Investigational Amlodipine The therapeutic efficacy of Natamycin can be increased when used in combination with Amlodipine. Approved Amphotericin B The therapeutic efficacy of Amphotericin B can be decreased when used in combination with Natamycin. Approved, Investigational Amrinone The therapeutic efficacy of Natamycin can be increased when used in combination with Amrinone. Approved Aranidipine The therapeutic efficacy of Natamycin can be increased when used in combination with Aranidipine. Approved, Investigational Atorvastatin The risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Atorvastatin. Approved Azelnidipine The therapeutic efficacy of Natamycin can be increased when used in combination with Azelnidipine. Approved, Investigational Azimilide The therapeutic efficacy of Natamycin can be increased when used in combination with Azimilide. Investigational Barnidipine The therapeutic efficacy of Natamycin can be increased when used in combination with Barnidipine. Approved BCG vaccine The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Natamycin. Investigational Bencyclane The therapeutic efficacy of Natamycin can be increased when used in combination with Bencyclane. Experimental Benidipine The therapeutic efficacy of Natamycin can be increased when used in combination with Benidipine. Approved, Investigational Bepridil The therapeutic efficacy of Natamycin can be increased when used in combination with Bepridil. Approved, Withdrawn Bioallethrin The therapeutic efficacy of Natamycin can be increased when used in combination with Bioallethrin. Approved, Experimental 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 therapeutic efficacy of Natamycin can be increased when used in combination with Carboxyamidotriazole. Investigational Caroverine The therapeutic efficacy of Natamycin can be increased when used in combination with Caroverine. Experimental Cerivastatin The risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Cerivastatin. Approved, Withdrawn Cilnidipine The therapeutic efficacy of Natamycin can be increased when used in combination with Cilnidipine. Approved, Investigational Cinnarizine The therapeutic efficacy of Natamycin can be increased when used in combination with Cinnarizine. Approved, Investigational Cisapride The serum concentration of Cisapride can be increased when it is combined with Natamycin. Approved, Investigational, Withdrawn Clevidipine The therapeutic efficacy of Natamycin can be increased when used in combination with Clevidipine. Approved, Investigational Cyclandelate The therapeutic efficacy of Natamycin can be increased when used in combination with Cyclandelate. Approved Cyclosporine The metabolism of Cyclosporine can be decreased when combined with Natamycin. Approved, Investigational, Vet Approved Darodipine The therapeutic efficacy of Natamycin can be increased when used in combination 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 therapeutic efficacy of Natamycin can be increased when used in combination with Diltiazem. Approved, Investigational Docetaxel The metabolism of Docetaxel can be decreased when combined with Natamycin. Approved, Investigational Dofetilide The serum concentration of Dofetilide can be increased when it is combined with Natamycin. Approved, Investigational Dotarizine The therapeutic efficacy of Natamycin can be increased when used in combination with Dotarizine. Investigational Efonidipine The therapeutic efficacy of Natamycin can be increased when used in combination with Efonidipine. Approved, Investigational Eperisone The therapeutic efficacy of Natamycin can be increased when used in combination with Eperisone. Approved, Investigational Ethosuximide The therapeutic efficacy of Natamycin can be increased when used in combination with Ethosuximide. Approved Etravirine The serum concentration of Etravirine can be increased when it is combined with Natamycin. Approved Felodipine The therapeutic efficacy of Natamycin can be increased when used in combination with Felodipine. Approved, Investigational Fendiline The therapeutic efficacy of Natamycin can be increased when used in combination with Fendiline. Withdrawn Fish oil The therapeutic efficacy of Natamycin can be increased when used in combination with Fish oil. Approved, Nutraceutical Flunarizine The therapeutic efficacy of Natamycin can be increased when used in combination with Flunarizine. Approved Fluspirilene The therapeutic efficacy of Natamycin can be increased when used in combination with Fluspirilene. Approved, Investigational Fluvastatin The risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Fluvastatin. Approved Fosphenytoin The serum concentration of Natamycin can be decreased when it is combined with Fosphenytoin. Approved, Investigational Gabapentin The therapeutic efficacy of Natamycin can be increased when used in combination with Gabapentin. Approved, Investigational Gallopamil The therapeutic efficacy of Natamycin can be increased when used in combination with Gallopamil. Investigational Isradipine The therapeutic efficacy of Natamycin can be increased when used in combination with Isradipine. Approved, Investigational Lacidipine The therapeutic efficacy of Natamycin can be increased when used in combination with Lacidipine. Approved, Investigational Lamotrigine The therapeutic efficacy of Natamycin can be increased when used in combination with Lamotrigine. Approved, Investigational Lercanidipine The therapeutic efficacy of Natamycin can be increased when used in combination with Lercanidipine. Approved, Investigational Levetiracetam The therapeutic efficacy of Natamycin can be increased when used in combination with Levetiracetam. Approved, Investigational Lidoflazine The therapeutic efficacy of Natamycin can be increased when used in combination with Lidoflazine. Experimental Loperamide The therapeutic efficacy of Natamycin can be increased when used in combination with Loperamide. Approved Losartan The metabolism of Losartan can be decreased when combined with Natamycin. Approved Lovastatin The risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Lovastatin. Approved, Investigational Magnesium sulfate The therapeutic efficacy of Natamycin can be increased when used in combination with Magnesium sulfate. Approved, Investigational, Vet Approved Manidipine The therapeutic efficacy of Natamycin can be increased when used in combination with Manidipine. Approved, Investigational Menthol The therapeutic efficacy of Natamycin can be increased when used in combination with Menthol. Approved Methsuximide The therapeutic efficacy of Natamycin can be increased when used in combination with Methsuximide. Approved Mevastatin The risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Mevastatin. Experimental Mibefradil The therapeutic efficacy of Natamycin can be increased when used in combination with Mibefradil. Investigational, Withdrawn Naftopidil The therapeutic efficacy of Natamycin can be increased when used in combination with Naftopidil. Investigational Nicardipine The therapeutic efficacy of Natamycin can be increased when used in combination with Nicardipine. Approved, Investigational Nifedipine The therapeutic efficacy of Natamycin can be increased when used in combination with Nifedipine. Approved Niguldipine The therapeutic efficacy of Natamycin can be increased when used in combination with Niguldipine. Experimental Niludipine The therapeutic efficacy of Natamycin can be increased when used in combination with Niludipine. Experimental Nilvadipine The therapeutic efficacy of Natamycin can be increased when used in combination with Nilvadipine. Approved, Investigational Nimesulide The therapeutic efficacy of Natamycin can be increased when used in combination with Nimesulide. Approved, Investigational, Withdrawn Nimodipine The therapeutic efficacy of Natamycin can be increased when used in combination with Nimodipine. Approved, Investigational Nisoldipine The therapeutic efficacy of Natamycin can be increased when used in combination with Nisoldipine. Approved Nitrendipine The therapeutic efficacy of Natamycin can be increased when used in combination with Nitrendipine. Approved, Investigational Nylidrin The therapeutic efficacy of Natamycin can be increased when used in combination with Nylidrin. Approved Otilonium The therapeutic efficacy of Natamycin can be increased when used in combination with Otilonium. Experimental, Investigational 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 Pinaverium The therapeutic efficacy of Natamycin can be increased when used in combination with Pinaverium. Approved Pitavastatin The risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Pitavastatin. Approved Pravastatin The risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Pravastatin. Approved Prenylamine The therapeutic efficacy of Natamycin can be increased when used in combination with Prenylamine. Withdrawn Progesterone The absorption of Progesterone can be decreased when combined with Natamycin. Approved, Vet Approved Quinidine The serum concentration of Quinidine can be increased when it is combined with Natamycin. Approved, Investigational Ranolazine The serum concentration of Ranolazine can be increased when it is combined with Natamycin. Approved, Investigational Rifabutin The serum concentration of Rifabutin can be increased when it is combined with Natamycin. Approved, Investigational 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, Investigational Rifaximin The serum concentration of Rifaximin can be increased when it is combined with Natamycin. Approved, Investigational Rosuvastatin The risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Rosuvastatin. Approved Seletracetam The therapeutic efficacy of Natamycin can be increased when used in combination with Seletracetam. Investigational Simvastatin The risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Simvastatin. Approved 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 Terodiline The therapeutic efficacy of Natamycin can be increased when used in combination with Terodiline. Experimental Tetrahydropalmatine The therapeutic efficacy of Natamycin can be increased when used in combination with Tetrahydropalmatine. Investigational Tolfenamic Acid The therapeutic efficacy of Natamycin can be increased when used in combination with Tolfenamic Acid. Approved, Investigational Tranilast The therapeutic efficacy of Natamycin can be increased when used in combination with Tranilast. Approved, Investigational Trimebutine The therapeutic efficacy of Natamycin can be increased when used in combination with Trimebutine. Approved Trimethadione The therapeutic efficacy of Natamycin can be increased when used in combination with Trimethadione. Approved Verapamil The therapeutic efficacy of Natamycin can be increased when used in combination with Verapamil. Approved Vinpocetine The therapeutic efficacy of Natamycin can be increased when used in combination with Vinpocetine. Investigational WIN 55212-2 The therapeutic efficacy of Natamycin can be increased when used in combination with WIN 55212-2. Experimental Ziconotide The therapeutic efficacy of Natamycin can be increased when used in combination with Ziconotide. Approved Zolpidem The serum concentration of Zolpidem can be increased when it is combined with Natamycin. Approved Zonisamide The therapeutic efficacy of Natamycin can be increased when used in combination with Zonisamide. Approved, Investigational - 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
- KEGG Drug
- D00884
- KEGG Compound
- C08073
- PubChem Compound
- 5284447
- PubChem Substance
- 46509171
- ChemSpider
- 10468784
- BindingDB
- 50370755
- ChEMBL
- CHEMBL1200656
- Therapeutic Targets Database
- DAP001331
- PharmGKB
- PA164744325
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Natamycin
- ATC Codes
- D01AA02 — Natamycin
- D01AA — Antibiotics
- D01A — ANTIFUNGALS FOR TOPICAL USE
- D01 — ANTIFUNGALS FOR DERMATOLOGICAL USE
- D — DERMATOLOGICALS
- A07AA — Antibiotics
- A07A — INTESTINAL ANTIINFECTIVES
- A07 — ANTIDIARRHEALS, INTESTINAL ANTIINFLAMMATORY/ANTIINFECTIVE AGENTS
- A — ALIMENTARY TRACT AND METABOLISM
- G01AA — Antibiotics
- G01A — ANTIINFECTIVES AND ANTISEPTICS, EXCL. COMBINATIONS WITH CORTICOSTEROIDS
- G01 — GYNECOLOGICAL ANTIINFECTIVES AND ANTISEPTICS
- G — GENITO URINARY SYSTEM AND SEX HORMONES
Clinical Trials
- 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS 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 show 13 more
- Substituents
- Aminoglycoside core / Macrolide / Hexose monosaccharide / O-glycosyl compound / Glycosyl compound / Beta-hydroxy acid / Hydroxy acid / Monosaccharide / Dicarboxylic acid or derivatives / Oxane show 29 more
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- Not Available
Targets
1. Ergosterol
Yes
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 June 02, 2018 06:41