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
  • Capreomicina
  • Capreomycin
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
Capastat sulfateInjection, powder, for solution1 g/2mLIntramuscular; IntravenousEli Lilly & Co. Ltd.1971-10-012011-06-30Us
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][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

Pharmacology

Indication

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

Associated Conditions
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
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Capreomycin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Capreomycin is combined with (S)-Warfarin.
1,10-PhenanthrolineThe therapeutic efficacy of 1,10-Phenanthroline can be decreased when used in combination with Capreomycin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Capreomycin is combined with 4-hydroxycoumarin.
AbacavirAbacavir may decrease the excretion rate of Capreomycin which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Capreomycin which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Capreomycin which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Capreomycin which could result in a higher serum level.
AcenocoumarolThe risk or severity of bleeding can be increased when Capreomycin is combined with Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Capreomycin which could result in a higher serum level.
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
HMDB0014459
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 / Tuberculosis Infection1
Not AvailableRecruitingNot AvailableTuberculosis Infection1
Not AvailableRecruitingTreatmentDrug-resistant Tuberculosis / Tuberculosis Infection / Tuberculosis, Multidrug Resistant1

Pharmacoeconomics

Manufacturers
  • Akorn inc
Packagers
  • Akorn Inc.
  • Eli Lilly & Co.
Dosage forms
FormRouteStrength
Powder, for solutionIntramuscular1 g
Injection, powder, for solutionIntramuscular; Intravenous1 g/2mL
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 14, 2018 16:24