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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyIdentification
- 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 Natamycin (DB00826)
- 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/1mL 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
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- Dermatologicals
- Genito Urinary System and Sex Hormones
- Gynecological Antiinfectives and Antiseptics
- Intestinal Antiinfectives
- Lactones
- Macrolides
- Ophthalmologicals
- Polyene Antifungal
- Polyene Antimicrobial
- Polyenes
- 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 Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Natamycin. Approved, Investigational Alprazolam The serum concentration of Alprazolam can be increased when it is combined with Natamycin. Approved, Illicit, Investigational 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 Atorvastatin The risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Atorvastatin. Approved Azimilide The therapeutic efficacy of Natamycin can be increased when used in combination with Azimilide. Investigational BCG vaccine The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Natamycin. Investigational Bromocriptine The serum concentration of Bromocriptine can be increased when it is combined with Natamycin. Approved, Investigational 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 Caffeine The metabolism of Caffeine can be decreased when combined with Natamycin. Approved Carbamazepine The metabolism of Carbamazepine can be decreased when combined with Natamycin. Approved, Investigational Cerivastatin The risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Cerivastatin. Approved, Withdrawn Cisapride The serum concentration of Cisapride can be increased when it is combined with Natamycin. Approved, Investigational, Withdrawn Cyclosporine The metabolism of Cyclosporine can be decreased when combined with Natamycin. Approved, Investigational, Vet Approved Didanosine Didanosine can cause a decrease in the absorption of Natamycin resulting in a reduced serum concentration and potentially a decrease in efficacy. Approved 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 Etravirine The serum concentration of Etravirine can be increased when it is combined with Natamycin. Approved Fosphenytoin The serum concentration of Natamycin can be decreased when it is combined with Fosphenytoin. Approved, Investigational Ganciclovir The metabolism of Ganciclovir can be decreased when combined with Natamycin. Approved, Investigational Hydrocodone The metabolism of Hydrocodone can be decreased when combined with Natamycin. Approved, Illicit, Investigational Lovastatin The risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Lovastatin. Approved, Investigational Mevastatin The risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Mevastatin. Experimental Picosulfuric acid The therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Natamycin. Approved Pitavastatin The risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Pitavastatin. Approved 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 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 Solifenacin The metabolism of Solifenacin can be decreased when combined with Natamycin. 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 Valaciclovir The metabolism of Valaciclovir can be decreased when combined with Natamycin. Approved, Investigational Warfarin The serum concentration of Warfarin 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
- 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/1mL - 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]
Enzymes
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- No
- 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 react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Kuper JI, D'Aprile M: Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease. Clin Pharmacokinet. 2000 Sep;39(3):203-14. [PubMed:11020135]
Drug created on June 13, 2005 07:24 / Updated on September 13, 2018 15:43