Gramicidin D

Identification

Summary

Gramicidin D is a bactericidal antibiotic used in the treatment of dermatological and ophthalmic infections.

Brand Names
Sofracort, Soframycin, Triple Antibiotic, Viaderm Kc
Generic Name
Gramicidin D
DrugBank Accession Number
DB00027
Background

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, which assemble inside of the hydrophobic interior of the cellular lipid bilayer to form a β-helix. Active against most Gram-positive bacteria and some Gram-negative organisms, Gramicidin D is used primarily as a topical antibiotic and is also found in Polysporin ophthalmic solution.

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 1811.253
Monoisotopic: 1810.033419343
Chemical Formula
C96H135N19O16
Synonyms
  • Bacillus brevis gramicidin D
  • Gramicidin
  • Gramicidin A
  • Gramicidin B
  • Gramicidin C
  • Gramicidina
  • Gramicidine

Pharmacology

Indication

For treatment of skin lesions, surface wounds and eye infections.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatAllergic skin reactionCombination Product in combination with: Framycetin (DB00452), Desoximetasone (DB00547)•••••••••••••••••••••• •• ••••••••••••••••••••
Used in combination to treatConjunctivitisCombination Product in combination with: Neomycin (DB00994), Polymyxin B (DB00781)••• •••
Used in combination to treatConjunctivitis allergicCombination Product in combination with: Framycetin (DB00452), Dexamethasone (DB01234)•••••••••••••••••••• • •••••
Used in combination to treatConjunctivitis infectiveCombination Product in combination with: Dexamethasone (DB01234), Framycetin (DB00452)•••••••••••••••••••• • •••••
Used in combination to treatCorneal inflammationCombination Product in combination with: Polymyxin B (DB00781), Neomycin (DB00994)••• •••
Contraindications & Blackbox Warnings
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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

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcenocoumarolThe risk or severity of bleeding can be increased when Gramicidin D is combined with Acenocoumarol.
AmbroxolThe risk or severity of methemoglobinemia can be increased when Gramicidin D is combined with Ambroxol.
ArticaineThe risk or severity of methemoglobinemia can be increased when Gramicidin D is combined with Articaine.
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Gramicidin D.
BenzocaineThe risk or severity of methemoglobinemia can be increased when Gramicidin D is combined with Benzocaine.
Food Interactions
No interactions found.

Products

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International/Other Brands
Sofradex (Sanofi)
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Antibiotic CreamGramicidin D (0.25 mg / g) + Polymyxin B sulfate (10000 unit / g)CreamTopicalCanadian Custom Packaging Company2012-03-222020-09-11Canada flag
Antibiotic CreamGramicidin D (0.25 mg / g) + Polymyxin B sulfate (10000 unit / g)CreamTopicalCellchem Pharmaceuticals Inc.2009-12-23Not applicableCanada flag
Antibiotic CreamGramicidin D (0.25 mg / g) + Polymyxin B sulfate (10000 unit / g)CreamTopicalTechnilab Pharma Inc.1998-11-032005-08-05Canada flag
Antibiotic Cream for KidsGramicidin D (0.25 mg / g) + Lidocaine hydrochloride (50 mg / g) + Polymyxin B sulfate (10000 unit / g)CreamTopicalCellchem Pharmaceuticals Inc.Not applicableNot applicableCanada flag
Antibiotic Cream for KidsGramicidin D (0.25 mg / g) + Lidocaine hydrochloride (50 mg / g) + Polymyxin B sulfate (10000 unit / g)CreamTopicalTaro Pharmaceuticals, Inc.2009-07-30Not applicableCanada flag

Categories

ATC Codes
R02AB30 — Gramicidin
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
3-alkylindole / Alanine or derivatives / Alcohol / Alkanolamine / Alpha peptide / Alpha-amino acid amide / Alpha-amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Benzenoid
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Pseudomonas aeruginosa
  • Streptococcus pneumoniae
  • Streptococcus agalactiae
  • Neisseria meningitidis
  • Haemophilus influenzae
  • Neisseria gonorrhoeae
  • Escherichia coli
  • Staphylococcus aureus
  • Klebsiella
  • Enterobacter

Chemical Identifiers

UNII
5IE62321P4
CAS number
1405-97-6
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

References

Synthesis Reference

U.S.Patent 2,534,541.

General References
  1. 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. [Article]
  2. 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. [Article]
  3. 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. [Article]
KEGG Drug
D04369
PubChem Compound
45267103
PubChem Substance
46507412
ChemSpider
24623445
RxNav
5011
ChEMBL
CHEMBL557217
Therapeutic Targets Database
DAP001327
PharmGKB
PA449808
Wikipedia
Gramicidin
MSDS
Download (71.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Unknown StatusTreatmentHordeolum1
Not AvailableWithdrawnPreventionBloodstream Infections (BSI) / Skin Diseases, Infectious1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Johnson & Johnson Healthcare
  • Monarch Pharmacy
  • Professional Co.
Dosage Forms
FormRouteStrength
SolutionAuricular (otic); Ophthalmic
Solution / dropsAuricular (otic)
Solution / dropsOphthalmic
SolutionOphthalmic
SolutionOphthalmic0.025 mg
LiquidAuricular (otic); Ophthalmic
OintmentOphthalmic
Solution / dropsAuricular (otic); Ophthalmic
Solution / dropsTopical
OintmentAuricular (otic); Ophthalmic
SprayNasal
SolutionOphthalmic25.000 mcg
OintmentTopical
LiquidOphthalmic
CreamTopical
Prices
Unit descriptionCostUnit
Gramicidin d powder240.0USD g
Neosporin gu irr 40 mg/ml amp23.12USD ml
Neosporin + pain relief cream0.32USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)229 °CNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0039 mg/mLALOGPS
logP4.38ALOGPS
logP5.96Chemaxon
logS-5.7ALOGPS
pKa (Strongest Acidic)11.56Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count16Chemaxon
Hydrogen Donor Count20Chemaxon
Polar Surface Area519.89 Å2Chemaxon
Rotatable Bond Count50Chemaxon
Refractivity492.33 m3·mol-1Chemaxon
Polarizability194.73 Å3Chemaxon
Number of Rings8Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-00lr-0220531900-85af15c0a08308ace16e
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-0010000900-200965bf767c46f6b7f8
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9742117600-846ddd0f7e6c9f79410a
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-3900418610-519bcf1badc9c8ee29a4
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-006x-8591202531-42019b3c4a014b8a318c
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0ac3-0930211120-e934c63071ef1d747568
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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
  1. 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. [Article]
  2. Borgnia MJ, Eytan GD, Assaraf YG: Competition of hydrophobic peptides, cytotoxic drugs, and chemosensitizers on a common P-glycoprotein pharmacophore as revealed by its ATPase activity. J Biol Chem. 1996 Feb 9;271(6):3163-71. [Article]
  3. Kondratov RV, Komarov PG, Becker Y, Ewenson A, Gudkov AV: Small molecules that dramatically alter multidrug resistance phenotype by modulating the substrate specificity of P-glycoprotein. Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):14078-83. doi: 10.1073/pnas.241314798. Epub 2001 Nov 13. [Article]

Drug created at June 13, 2005 13:24 / Updated at January 02, 2024 23:41