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Identification
NameCapreomycin
Accession NumberDB00314  (APRD00844)
TypeSmall Molecule
GroupsApproved
Description

Cyclic peptide antibiotic similar to viomycin. It is produced by Streptomyces capreolus. [PubChem]

Structure
Thumb
SynonymsNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Capastat Sulfateinjection, powder, for solution1 gintramuscular; intravenousAkorn2009-08-01Not AvailableUs
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
CapastatAkorn Incorporated
CapreomycinBristol-Myers Squibb
HelpomycinUnifarm
KapocinMacleods
LykocinLyka Labs Ltd.
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Capreomycin sulfate
Thumb
  • InChI Key: AJQVUIHGEOLMDY-SOCRLDLMNA-N
  • Monoisotopic Mass: 766.314033696
  • Average Mass: 766.784
DBSALT000443
CategoriesNot Available
CAS number11003-38-6
WeightAverage: 1321.4123
Monoisotopic: 1320.698394286
Chemical FormulaC50H88N28O15
InChI KeyVCOPTHOUUNAYKQ-WBTCAYNUSA-N
InChI
InChI=1S/C25H44N14O8.C25H44N14O7/c26-4-1-2-11(27)6-17(41)32-8-14-20(43)35-15(9-34-25(30)47)21(44)39-18(13-3-5-31-24(29)38-13)23(46)33-7-12(28)19(42)37-16(10-40)22(45)36-14;1-11-19(41)36-15(9-32-17(40)7-12(27)3-2-5-26)21(43)37-16(10-34-25(30)46)22(44)39-18(14-4-6-31-24(29)38-14)23(45)33-8-13(28)20(42)35-11/h9,11-14,16,18,40H,1-8,10,26-28H2,(H,32,41)(H,33,46)(H,35,43)(H,36,45)(H,37,42)(H,39,44)(H3,29,31,38)(H3,30,34,47);10-15,18H,2-9,26-28H2,1H3,(H,32,40)(H,33,45)(H,35,42)(H,36,41)(H,37,43)(H,39,44)(H3,29,31,38)(H3,30,34,46)/b15-9+;16-10+/t11-,12-,13+,14-,16-,18-;11-,12-,13-,14+,15-,18-/m00/s1
IUPAC Name
(3S)-3,6-diamino-N-{[(2S,5S,8E,11S,15S)-15-amino-11-[(4R)-2-amino-3,4,5,6-tetrahydropyrimidin-4-yl]-8-[(carbamoylamino)methylidene]-2-(hydroxymethyl)-3,6,9,12,16-pentaoxo-1,4,7,10,13-pentaazacyclohexadecan-5-yl]methyl}hexanamide; (3S)-3,6-diamino-N-{[(2S,5S,8E,11S,15S)-15-amino-11-[(4R)-2-amino-3,4,5,6-tetrahydropyrimidin-4-yl]-8-[(carbamoylamino)methylidene]-2-methyl-3,6,9,12,16-pentaoxo-1,4,7,10,13-pentaazacyclohexadecan-5-yl]methyl}hexanamide
SMILES
[H][C@@]1(CCN=C(N)N1)[C@]1([H])NC(=O)\C(NC(=O)[C@H](CNC(=O)C[C@@H](N)CCCN)NC(=O)[C@H](C)NC(=O)[C@@H](N)CNC1=O)=C/NC(N)=O.[H][C@@]1(CCN=C(N)N1)[C@]1([H])NC(=O)\C(NC(=O)[C@H](CNC(=O)C[C@@H](N)CCCN)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CNC1=O)=C/NC(N)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as hybrid peptides. These are compounds containing at least two different types of amino acids (alpha, beta, gamma, delta) linked to each other through a peptide bond.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentHybrid peptides
Alternative Parents
Substituents
  • Hybrid peptide
  • Macrolactam
  • Alpha-amino acid amide
  • Beta amino acid or derivatives
  • Alpha-amino acid or derivatives
  • Fatty acyl
  • N-acyl-amine
  • 1,4,5,6-tetrahydropyrimidine
  • Hydropyrimidine
  • Fatty amide
  • Vinylogous amide
  • Urea
  • Secondary carboxylic acid amide
  • Lactam
  • Guanidine
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary amine
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Alcohol
  • Aliphatic heteromonocyclic compound
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationUsed in the treatment of tuberculosis in combination with other drugs.
PharmacodynamicsCapreomycin is a member of the aminoglycoside family of antibiotics. These antibiotics have the ability to kill a wide variety of bacteria, including bacteria responsible for causing tuberculosis (TB).
Mechanism of actionLittle is known about capreomycin's exact mechanism of action, but it is thought to inhibit protein synthesis by binding to the 70S ribosomal unit. Capreomycin also binds to components in the bacterial cell which result in the production of abnormal proteins. These proteins are necessary for the bacteria's survival. Therefore the production of these abnormal proteins is ultimately fatal to the bacteria.
AbsorptionNot absorbed in significant quantities from the gastrointestinal tract and must be administered parenterally.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationWhen a 1–g dose of capreomycin was given intramuscularly to normal volunteers, 52% was excreted in the urine within 12 hours.
Half lifeNot Available
ClearanceNot Available
ToxicityHypokalemia, hypocalcemia, hypomagnesemia, and an electrolyte disturbance resembling Bartter's syndrome have been reported to occur in patients with capreomycin toxicity. The subcutaneous median lethal dose (LD50) in mice was 514 mg/kg.
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6871
Blood Brain Barrier-0.9287
Caco-2 permeable-0.6762
P-glycoprotein substrateSubstrate0.8642
P-glycoprotein inhibitor INon-inhibitor0.742
P-glycoprotein inhibitor IINon-inhibitor0.9864
Renal organic cation transporterNon-inhibitor0.7924
CYP450 2C9 substrateNon-substrate0.6651
CYP450 2D6 substrateNon-substrate0.8065
CYP450 3A4 substrateNon-substrate0.5716
CYP450 1A2 substrateNon-inhibitor0.9053
CYP450 2C9 substrateNon-inhibitor0.8828
CYP450 2D6 substrateNon-inhibitor0.9196
CYP450 2C19 substrateNon-inhibitor0.881
CYP450 3A4 substrateNon-inhibitor0.9435
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9907
Ames testNon AMES toxic0.6035
CarcinogenicityNon-carcinogens0.894
BiodegradationNot ready biodegradable0.991
Rat acute toxicity2.5199 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8741
hERG inhibition (predictor II)Non-inhibitor0.671
Pharmacoeconomics
Manufacturers
  • Akorn inc
Packagers
Dosage forms
FormRouteStrength
Injection, powder, for solutionintramuscular; intravenous1 g
Prices
Unit descriptionCostUnit
Capastat sulfate 1 gm vial25.54USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilitySoluble in water as disulfate salt.Not Available
logP-9.609Not Available
Predicted Properties
PropertyValueSource
logP-11ChemAxon
pKa (Strongest Acidic)10.62ChemAxon
pKa (Strongest Basic)10.3ChemAxon
Physiological Charge4ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count14ChemAxon
Polar Surface Area378.42 Å2ChemAxon
Rotatable Bond Count19ChemAxon
Refractivity162.2 m3·mol-1ChemAxon
Polarizability66.56 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Michael George Thomas, Elizabeth Anne Felnagle, Michelle Renee Rondon, Andrew David Berti, “Heterologous Production of Capreomycin and Generation of New Capreomycin Derivatives Through Metabolic Engineering.” U.S. Patent US20090104658, issued April 23, 2009.

US20090104658
General ReferenceNot Available
External Links
ATC CodesJ04AB30
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (204 KB)
MSDSDownload (131 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. 70S ribosome

Kind: protein group

Organism: Mycobacterium tuberculosis

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details

References:

  1. Stanley RE, Blaha G, Grodzicki RL, Strickler MD, Steitz TA: The structures of the anti-tuberculosis antibiotics viomycin and capreomycin bound to the 70S ribosome. Nat Struct Mol Biol. 2010 Mar;17(3):289-93. Epub 2010 Feb 14. Pubmed
  2. Johansen SK, Maus CE, Plikaytis BB, Douthwaite S: Capreomycin binds across the ribosomal subunit interface using tlyA-encoded 2’-O-methylations in 16S and 23S rRNAs. Mol Cell. 2006 Jul 21;23(2):173-82. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:09