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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyGramicidin D
Identification
- Name
- Gramicidin D
- Accession Number
- DB00027 (BTD00036, BIOD00036)
- Type
- Small Molecule
- Groups
- Approved
- Description
Gramcidin D is a heterogeneous mixture of three antibiotic compounds, gramicidins A, B and C, making up 80%, 6%, and 14% respectively all of which are obtained from the soil bacterial species Bacillus brevis and called collectively gramicidin D. Gramcidins are 15 residue peptides with alternating D and L amino acids. The peptides assemble inside of the hydrophobic interior of the cellular lipid bilayer to form a β-helix. The helix itself is not long enough to span the membrane but it dimerizes to form the elongated channel needed to span the whole membrane. Gramicidin D is used primarily as a topical antibiotic and is one of the three constituents of consumer antibiotic polysporin ophthalmic solution.
- Structure
Structure for DB00027 (Gramicidin D)
- Synonyms
- Bacillus brevis gramicidin D
- Gramicidin
- Gramicidin A
- Gramicidin B
- Gramicidin C
- Gramicidine
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Antibiotic Cream Gramicidin D (0.25 mg) + Polymyxin B Sulfate (10000 unit) Cream Topical Pharmetics (2011) Inc. 2009-12-23 Not applicable Canada 
Antibiotic Cream Gramicidin D (0.25 mg) + Polymyxin B Sulfate (10000 unit) Cream Topical Technilab Pharma Inc. 1998-11-03 2005-08-05 Canada Antibiotic Cream Gramicidin D (0.25 mg) + Polymyxin B Sulfate (10000 unit) Cream Topical Canadian Custom Packaging Company 2012-03-22 Not applicable Canada Antibiotic Cream for Kids Gramicidin D (0.25 mg) + Lidocaine hydrochloride (50 mg) + Polymyxin B Sulfate (10000 unit) Cream Topical Pharmetics (2011) Inc. Not applicable Not applicable Canada Antibiotic Cream for Kids Gramicidin D (0.25 mg) + Lidocaine hydrochloride (50 mg) + Polymyxin B Sulfate (10000 unit) Cream Topical Taro Pharmaceuticals, Inc. 2009-07-30 Not applicable Canada Antibiotic Cream Plus Pain Relief Gramicidin D (0.25 mg) + Lidocaine hydrochloride (50 mg) + Polymyxin B Sulfate (10000 unit) Cream Topical Pharmetics (2011) Inc. 2009-12-23 Not applicable Canada Antibiotic Cream Plus Pain Relief Gramicidin D (0.25 mg) + Lidocaine hydrochloride (40 mg) + Polymyxin B Sulfate (10000 unit) Cream Topical Canadian Custom Packaging Company 2012-04-09 Not applicable Canada Antibiotic Cream Plus Pain Relief for Kids Gramicidin D (0.25 mg) + Lidocaine hydrochloride (40 mg) + Polymyxin B Sulfate (10000 unit) Cream Topical Canadian Custom Packaging Company 2012-07-11 Not applicable Canada Antibiotic Drops Gramicidin D (0.025 mg) + Polymyxin B Sulfate (10000 unit) Solution Auricular (otic); Ophthalmic Sandoz Canada Incorporated 2017-06-01 Not applicable Canada Antibiotic Ear Drops Gramicidin D (0.025 mg) + Polymyxin B Sulfate (10000 unit) Solution / drops Auricular (otic) Sandoz Canada Incorporated 2017-09-01 Not applicable Canada - International/Other Brands
- Sofradex (Sanofi)
- Categories
- UNII
- 5IE62321P4
- CAS number
- 1405-97-6
- Weight
- Average: 1811.253
Monoisotopic: 1810.033419343 - Chemical Formula
- C96H135N19O16
- InChI Key
- NDAYQJDHGXTBJL-MWWSRJDJSA-N
- InChI
- InChI=1S/C96H135N19O16/c1-50(2)36-71(105-79(118)48-102-93(128)80(54(9)10)103-49-117)86(121)104-58(17)84(119)113-82(56(13)14)95(130)115-83(57(15)16)96(131)114-81(55(11)12)94(129)112-78(43-62-47-101-70-33-25-21-29-66(62)70)92(127)108-74(39-53(7)8)89(124)111-77(42-61-46-100-69-32-24-20-28-65(61)69)91(126)107-73(38-52(5)6)88(123)110-76(41-60-45-99-68-31-23-19-27-64(60)68)90(125)106-72(37-51(3)4)87(122)109-75(85(120)97-34-35-116)40-59-44-98-67-30-22-18-26-63(59)67/h18-33,44-47,49-58,71-78,80-83,98-101,116H,34-43,48H2,1-17H3,(H,97,120)(H,102,128)(H,103,117)(H,104,121)(H,105,118)(H,106,125)(H,107,126)(H,108,127)(H,109,122)(H,110,123)(H,111,124)(H,112,129)(H,113,119)(H,114,131)(H,115,130)/t58-,71+,72+,73+,74+,75-,76-,77-,78-,80-,81+,82+,83-/m0/s1
- IUPAC Name
- (2R)-N-[(1S)-1-{[(1R)-1-{[(1S)-1-{[(1R)-1-{[(1S)-1-{[(1R)-1-{[(1S)-1-{[(1R)-1-{[(1S)-1-{[(1R)-1-{[(1S)-1-[(2-hydroxyethyl)carbamoyl]-2-(1H-indol-3-yl)ethyl]carbamoyl}-3-methylbutyl]carbamoyl}-2-(1H-indol-3-yl)ethyl]carbamoyl}-3-methylbutyl]carbamoyl}-2-(1H-indol-3-yl)ethyl]carbamoyl}-3-methylbutyl]carbamoyl}-2-(1H-indol-3-yl)ethyl]carbamoyl}-2-methylpropyl]carbamoyl}-2-methylpropyl]carbamoyl}-2-methylpropyl]carbamoyl}ethyl]-2-{2-[(2S)-2-formamido-3-methylbutanamido]acetamido}-4-methylpentanamide
- SMILES
- CC(C)C[C@@H](NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)NCCO
Pharmacology
- Indication
For treatment of skin lesions, surface wounds and eye infections.
- Associated Conditions
- Pharmacodynamics
Gramicidin is particularly effective against gram-positive bacteria. Because the drug is highly hemolytic, it cannot be administered internally and so is used only on the skin as a lotion or ointment. It is used primarily in the treatment of infected surface wounds, and in eye, nose, and throat infections. It is normally given with two other antibiotics (neomycin and polymixin B) as an ophthalmic solution.
- Mechanism of action
Gramicidin D binds to and inserts itself into bacterial membranes (with a strong preference to gram-positive cell membranes). This results in membrane disruption and permeabilization (it acts as a channel). This leads to (i) loss of intracellular solutes (e.g., K+ and amino acids); (ii) dissipation of the transmembrane potential; (iii) inhibition of respiration; (iv) a reduction in ATP pools; and (v) inhibition of DNA, RNA, and protein synthesis, which leads to cell death.
- Absorption
- Not Available
- 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
- Pseudomonas aeruginosa
- Streptococcus pneumoniae
- Streptococcus agalactiae
- Neisseria meningitidis
- Haemophilus influenzae
- Neisseria gonorrhoeae
- Escherichia coli
- Staphylococcus aureus
- Klebsiella
- Enterobacter
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction Drug group Afatinib The serum concentration of Afatinib can be increased when it is combined with Gramicidin D. Approved BCG vaccine The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Gramicidin D. Investigational Bosutinib The serum concentration of Bosutinib can be increased when it is combined with Gramicidin D. Approved Brentuximab vedotin The serum concentration of Brentuximab vedotin can be increased when it is combined with Gramicidin D. Approved, Investigational Colchicine The serum concentration of Colchicine can be increased when it is combined with Gramicidin D. Approved Dabigatran etexilate The serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Gramicidin D. Approved Doxorubicin The serum concentration of Doxorubicin can be increased when it is combined with Gramicidin D. Approved, Investigational Edoxaban The serum concentration of Edoxaban can be increased when it is combined with Gramicidin D. Approved Everolimus The serum concentration of Everolimus can be increased when it is combined with Gramicidin D. Approved Ledipasvir The serum concentration of Ledipasvir can be increased when it is combined with Gramicidin D. Approved Naloxegol The serum concentration of Naloxegol can be increased when it is combined with Gramicidin D. Approved Pazopanib The serum concentration of Pazopanib can be increased when it is combined with Gramicidin D. Approved Picosulfuric acid The therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Gramicidin D. Approved Prucalopride The serum concentration of Prucalopride can be increased when it is combined with Gramicidin D. Approved Ranolazine The serum concentration of Ranolazine can be increased when it is combined with Gramicidin D. Approved, Investigational Rifaximin The serum concentration of Rifaximin can be increased when it is combined with Gramicidin D. Approved, Investigational Silodosin The serum concentration of Silodosin can be increased when it is combined with Gramicidin D. Approved Topotecan The serum concentration of Topotecan can be increased when it is combined with Gramicidin D. Approved, Investigational Vincristine The excretion of Vincristine can be decreased when combined with Gramicidin D. Approved, Investigational - Food Interactions
- Not Available
References
- Synthesis Reference
U.S.Patent 2,534,541.
- General References
- Ketchem RR, Lee KC, Huo S, Cross TA: Macromolecular structural elucidation with solid-state NMR-derived orientational constraints. J Biomol NMR. 1996 Jul;8(1):1-14. [PubMed:8810522]
- Townsley LE, Tucker WA, Sham S, Hinton JF: Structures of gramicidins A, B, and C incorporated into sodium dodecyl sulfate micelles. Biochemistry. 2001 Oct 2;40(39):11676-86. [PubMed:11570868]
- Burkhart BM, Gassman RM, Langs DA, Pangborn WA, Duax WL, Pletnev V: Gramicidin D conformation, dynamics and membrane ion transport. Biopolymers. 1999;51(2):129-44. [PubMed:10397797]
- External Links
- KEGG Drug
- D04369
- PubChem Compound
- 45267103
- PubChem Substance
- 46507412
- ChemSpider
- 24623445
- ChEMBL
- CHEMBL557217
- Therapeutic Targets Database
- DAP001327
- PharmGKB
- PA449808
- Wikipedia
- Gramicidin_D
- ATC Codes
- R02AB30 — Gramicidin
- MSDS
- Download (71.9 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Unknown Status Treatment Hordeolum 1 Not Available Completed Treatment Nasal Carriers of Staphylococcus Aureus 1 Not Available Withdrawn Prevention Blood Stream Infections / Skin Diseases, Infectious 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Johnson & Johnson Healthcare
- Monarch Pharmacy
- Professional Co.
- Dosage forms
Form Route Strength Solution / drops Auricular (otic) Solution / drops Ophthalmic Solution Ophthalmic Solution Auricular (otic); Ophthalmic Liquid Ophthalmic Liquid Auricular (otic); Ophthalmic Solution / drops Auricular (otic); Ophthalmic Solution / drops Topical Ointment Auricular (otic); Ophthalmic Spray Nasal Cream Topical Ointment Topical - Prices
Unit description Cost Unit Gramicidin d powder 240.0USD g Neosporin gu irr 40 mg/ml amp 23.12USD ml Neosporin + pain relief cream 0.32USD g DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) 229 °C Not Available - Predicted Properties
Property Value Source Water Solubility 0.0039 mg/mL ALOGPS logP 4.38 ALOGPS logP 5.96 ChemAxon logS -5.7 ALOGPS pKa (Strongest Acidic) 11.56 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 16 ChemAxon Hydrogen Donor Count 20 ChemAxon Polar Surface Area 519.89 Å2 ChemAxon Rotatable Bond Count 50 ChemAxon Refractivity 492.33 m3·mol-1 ChemAxon Polarizability 194.73 Å3 ChemAxon Number of Rings 8 ChemAxon Bioavailability 0 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Taxonomy
- Description
- This compound belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues.
- Kingdom
- Organic compounds
- Super Class
- Organic Polymers
- Class
- Polypeptides
- Sub Class
- Not Available
- Direct Parent
- Polypeptides
- Alternative Parents
- Peptides / Leucine and derivatives / Valine and derivatives / N-acyl-alpha amino acids and derivatives / Tryptamines and derivatives / N-formyl-alpha amino acids / Alpha amino acid amides / Alanine and derivatives / 3-alkylindoles / N-acylethanolamines show 10 more
- Substituents
- Polypeptide / Alpha peptide / Leucine or derivatives / Valine or derivatives / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / N-formyl-alpha-amino acid / N-formyl-alpha amino acid or derivatives / Triptan / Alanine or derivatives show 29 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
Transporters
- 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
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [PubMed:14985103]
Drug created on June 13, 2005 07:24 / Updated on June 02, 2018 06:29