Identification

Name
Capreomycin
Accession Number
DB00314  (APRD00844)
Type
Small Molecule
Groups
Approved
Description

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

Structure
Thumb
Synonyms
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Capreomycin sulfate9H8D3J7V211405-37-4AJQVUIHGEOLMDY-SOCRLDLMSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Capastat PWS IM 1g VialPowder, for solution1 gIntramuscularEli Lilly & Co. Ltd.1994-12-311997-08-13Canada
Capastat SulfateInjection, powder, for solution1 g/1Intramuscular; IntravenousAkorn2009-08-01Not applicableUs
International/Other Brands
Capastat (Akorn Incorporated) / Capreomycin (Bristol-Myers Squibb) / Helpomycin (Unifarm) / Kapocin (Macleods) / Lykocin (Lyka Labs Ltd.)
Categories
UNII
232HYX66HC
CAS number
11003-38-6
Weight
Average: 1321.4123
Monoisotopic: 1320.698394286
Chemical Formula
C50H88N28O15
InChI Key
VCOPTHOUUNAYKQ-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][[email protected]@]1(CCN=C(N)N1)[[email protected]]1([H])NC(=O)\C(NC(=O)[[email protected]](CNC(=O)C[[email protected]@H](N)CCCN)NC(=O)[[email protected]](C)NC(=O)[[email protected]@H](N)CNC1=O)=C/NC(N)=O.[H][[email protected]@]1(CCN=C(N)N1)[[email protected]]1([H])NC(=O)\C(NC(=O)[[email protected]](CNC(=O)C[[email protected]@H](N)CCCN)NC(=O)[[email protected]](CO)NC(=O)[[email protected]@H](N)CNC1=O)=C/NC(N)=O

Pharmacology

Indication

Used in the treatment of tuberculosis in combination with other drugs.

Structured Indications
Pharmacodynamics

Capreomycin 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 action

Little 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.

TargetActionsOrganism
A70S ribosome
inhibitor
Mycobacterium tuberculosis
Absorption

Not absorbed in significant quantities from the gastrointestinal tract and must be administered parenterally.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

When a 1–g dose of capreomycin was given intramuscularly to normal volunteers, 52% was excreted in the urine within 12 hours.

Half life
Not Available
Clearance
Not Available
Toxicity

Hypokalemia, 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AclarubicinCapreomycin may increase the neuromuscular blocking activities of Aclarubicin.Investigational
AlcuroniumCapreomycin may increase the neuromuscular blocking activities of Alcuronium.Experimental
AldoxorubicinCapreomycin may increase the neuromuscular blocking activities of Aldoxorubicin.Investigational
AmikacinCapreomycin may increase the neuromuscular blocking activities of Amikacin.Approved, Vet Approved
AmrubicinCapreomycin may increase the neuromuscular blocking activities of Amrubicin.Approved, Investigational
AnnamycinCapreomycin may increase the neuromuscular blocking activities of Annamycin.Investigational
ApramycinCapreomycin may increase the neuromuscular blocking activities of Apramycin.Experimental, Vet Approved
ArbekacinCapreomycin may increase the neuromuscular blocking activities of Arbekacin.Approved, Investigational
AtracuriumCapreomycin may increase the neuromuscular blocking activities of Atracurium.Experimental, Investigational
Atracurium besylateCapreomycin may increase the neuromuscular blocking activities of Atracurium besylate.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Capreomycin.Investigational
BekanamycinCapreomycin may increase the neuromuscular blocking activities of Bekanamycin.Experimental
CisatracuriumCapreomycin may increase the neuromuscular blocking activities of Cisatracurium.Approved, Experimental
Cisatracurium besylateCapreomycin may increase the neuromuscular blocking activities of Cisatracurium besylate.Approved
ColistimethateCapreomycin may increase the neuromuscular blocking activities of Colistimethate.Approved, Vet Approved
DaunorubicinCapreomycin may increase the neuromuscular blocking activities of Daunorubicin.Approved
DecamethoniumCapreomycin may increase the neuromuscular blocking activities of Decamethonium.Approved
DibekacinCapreomycin may increase the neuromuscular blocking activities of Dibekacin.Experimental
DihydrostreptomycinCapreomycin may increase the neuromuscular blocking activities of Dihydrostreptomycin.Investigational, Vet Approved
Domoic AcidCapreomycin may increase the neuromuscular blocking activities of Domoic Acid.Experimental
Doxacurium chlorideCapreomycin may increase the neuromuscular blocking activities of Doxacurium chloride.Approved
DoxorubicinCapreomycin may increase the neuromuscular blocking activities of Doxorubicin.Approved, Investigational
EpirubicinCapreomycin may increase the neuromuscular blocking activities of Epirubicin.Approved
FramycetinCapreomycin may increase the neuromuscular blocking activities of Framycetin.Approved
GallamineCapreomycin may increase the neuromuscular blocking activities of Gallamine.Experimental
Gallamine TriethiodideCapreomycin may increase the neuromuscular blocking activities of Gallamine Triethiodide.Approved
GeneticinCapreomycin may increase the neuromuscular blocking activities of Geneticin.Experimental
GentamicinCapreomycin may increase the neuromuscular blocking activities of Gentamicin.Approved, Vet Approved
GENTAMICIN C1ACapreomycin may increase the neuromuscular blocking activities of GENTAMICIN C1A.Experimental
GPX-150Capreomycin may increase the neuromuscular blocking activities of GPX-150.Investigational
Hygromycin BCapreomycin may increase the neuromuscular blocking activities of Hygromycin B.Vet Approved
IdarubicinCapreomycin may increase the neuromuscular blocking activities of Idarubicin.Approved
IsepamicinCapreomycin may increase the neuromuscular blocking activities of Isepamicin.Experimental
KanamycinCapreomycin may increase the neuromuscular blocking activities of Kanamycin.Approved, Investigational, Vet Approved
MecamylamineCapreomycin may increase the neuromuscular blocking activities of Mecamylamine.Approved
MetocurineCapreomycin may increase the neuromuscular blocking activities of Metocurine.Approved
Metocurine IodideCapreomycin may increase the neuromuscular blocking activities of Metocurine Iodide.Withdrawn
MetrizamideCapreomycin may increase the neuromuscular blocking activities of Metrizamide.Approved
MicronomicinCapreomycin may increase the neuromuscular blocking activities of Micronomicin.Experimental
MivacuriumCapreomycin may increase the neuromuscular blocking activities of Mivacurium.Approved
NeamineCapreomycin may increase the neuromuscular blocking activities of Neamine.Experimental
NeomycinCapreomycin may increase the neuromuscular blocking activities of Neomycin.Approved, Vet Approved
NeosaxitoxinCapreomycin may increase the neuromuscular blocking activities of Neosaxitoxin.Investigational
NetilmicinCapreomycin may increase the neuromuscular blocking activities of Netilmicin.Approved, Investigational
PancuroniumCapreomycin may increase the neuromuscular blocking activities of Pancuronium.Approved
ParomomycinCapreomycin may increase the neuromuscular blocking activities of Paromomycin.Approved, Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Capreomycin.Approved
PipecuroniumCapreomycin may increase the neuromuscular blocking activities of Pipecuronium.Approved
PirarubicinCapreomycin may increase the neuromuscular blocking activities of Pirarubicin.Investigational
PlazomicinCapreomycin may increase the neuromuscular blocking activities of Plazomicin.Investigational
PlicamycinCapreomycin may increase the neuromuscular blocking activities of Plicamycin.Approved, Investigational, Withdrawn
Polymyxin B SulfateCapreomycin may increase the neuromuscular blocking activities of Polymyxin B Sulfate.Approved, Vet Approved
PuromycinCapreomycin may increase the neuromuscular blocking activities of Puromycin.Experimental
PyrantelCapreomycin may increase the neuromuscular blocking activities of Pyrantel.Approved, Vet Approved
RapacuroniumCapreomycin may increase the neuromuscular blocking activities of Rapacuronium.Withdrawn
RibostamycinCapreomycin may increase the neuromuscular blocking activities of Ribostamycin.Approved, Investigational
RocuroniumCapreomycin may increase the neuromuscular blocking activities of Rocuronium.Approved
SabarubicinCapreomycin may increase the neuromuscular blocking activities of Sabarubicin.Investigational
SisomicinCapreomycin may increase the neuromuscular blocking activities of Sisomicin.Investigational
SP1049CCapreomycin may increase the neuromuscular blocking activities of SP1049C.Investigational
SpectinomycinCapreomycin may increase the neuromuscular blocking activities of Spectinomycin.Approved, Investigational, Vet Approved
StreptomycinCapreomycin may increase the neuromuscular blocking activities of Streptomycin.Approved, Vet Approved
StreptozocinCapreomycin may increase the neuromuscular blocking activities of Streptozocin.Approved
SuccinylcholineCapreomycin may increase the neuromuscular blocking activities of Succinylcholine.Approved
TobramycinCapreomycin may increase the neuromuscular blocking activities of Tobramycin.Approved, Investigational
TubocurarineCapreomycin may increase the neuromuscular blocking activities of Tubocurarine.Approved
ValrubicinCapreomycin may increase the neuromuscular blocking activities of Valrubicin.Approved
VecuroniumCapreomycin may increase the neuromuscular blocking activities of Vecuronium.Approved
Zoptarelin doxorubicinCapreomycin may increase the neuromuscular blocking activities of Zoptarelin doxorubicin.Investigational
ZorubicinCapreomycin may increase the neuromuscular blocking activities of Zorubicin.Experimental
Food Interactions
Not 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 References
Not Available
External Links
Human Metabolome Database
HMDB14459
KEGG Drug
D00135
KEGG Compound
C01790
PubChem Compound
3000502
PubChem Substance
46508514
ChemSpider
2272094
ChEBI
3371
ChEMBL
CHEMBL2303634
Therapeutic Targets Database
DAP000892
PharmGKB
PA164746226
Drugs.com
Drugs.com Drug Page
Wikipedia
Capreomycin
ATC Codes
J04AB30 — Capreomycin
FDA label
Download (204 KB)
MSDS
Download (131 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis1
Not AvailableRecruitingTreatmentDrug-resistant Tuberculosis / Tuberculosis / Tuberculosis, Multidrug Resistant1

Pharmacoeconomics

Manufacturers
  • Akorn inc
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntramuscular1 g
Injection, powder, for solutionIntramuscular; Intravenous1 g/1
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.
Patents
Not Available

Properties

State
Solid
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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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 inhibitorNon-inhibitor0.8828
CYP450 2D6 inhibitorNon-inhibitor0.9196
CYP450 2C19 inhibitorNon-inhibitor0.881
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Oligopeptides
Alternative Parents
Cyclic peptides / Macrolactams / Alpha amino acid amides / Beta amino acids and derivatives / N-acyl amines / Hydropyrimidines / Vinylogous amides / Secondary carboxylic acid amides / Ureas / Guanidines
show 10 more
Substituents
Alpha-oligopeptide / Cyclic alpha peptide / Macrolactam / Alpha-amino acid amide / Beta amino acid or derivatives / Alpha-amino acid or derivatives / Fatty amide / Hydropyrimidine / Fatty acyl / 1,4,5,6-tetrahydropyrimidine
show 28 more
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

1. 70S ribosome
Kind
Protein group
Organism
Mycobacterium tuberculosis
Pharmacological action
Yes
Actions
Inhibitor
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. doi: 10.1038/nsmb.1755. Epub 2010 Feb 14. [PubMed:20154709]
  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:16857584]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 17:14