Identification

Name
Spectinomycin
Accession Number
DB00919  (APRD01232)
Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Description

An antibiotic produced by Streptomyces spectabilis. It is active against gram-negative bacteria and used for the treatment of gonorrhea.

Structure
Thumb
Synonyms
  • Actinospectacina
  • Espectinomicina
  • SCM
  • Spectinomicina
  • Spectinomycine
  • Spectinomycinum
External IDs
Antibiotic 2233wp / CHX-3101
Product Ingredients
IngredientUNIICASInChI Key
Spectinomycin dihydrochloride pentahydrateNot AvailableNot AvailableNot applicable
Spectinomycin hydrochlorideHWT06H303Z22189-32-8BIPVCOUVVAMJMZ-MTTMTQIXSA-N
Spectinomycin hydrochloride pentahydrateNot AvailableNot AvailableNot applicable
Spectinomycin sulfateBZ0H4TLF9X23312-56-3XGBFWQUQYQIFLB-MTTMTQIXSA-N
Spectinomycin sulfate tetrahydrateYS91P5491864058-48-6OBZDRKHRQYPQDZ-SACNDDTHSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TrobicinKit400 mg/1mLPharmacia & Upjohn Inc1971-07-012006-05-31Us
Trobicin Inj 400mg/mlPowder, for solution400 mgIntramuscularUpjohn1972-12-311997-08-28Canada
International/Other Brands
Actinospectacin / Spectam / Togamycin / Trobicin
Categories
UNII
93AKI1U6QF
CAS number
1695-77-8
Weight
Average: 332.3496
Monoisotopic: 332.158351132
Chemical Formula
C14H24N2O7
InChI Key
UNFWWIHTNXNPBV-WXKVUWSESA-N
InChI
InChI=1S/C14H24N2O7/c1-5-4-6(17)14(20)13(21-5)22-12-10(19)7(15-2)9(18)8(16-3)11(12)23-14/h5,7-13,15-16,18-20H,4H2,1-3H3/t5-,7-,8+,9+,10+,11-,12-,13+,14+/m1/s1
IUPAC Name
(1R,3S,5R,8R,10R,11S,12S,13R,14S)-8,12,14-trihydroxy-5-methyl-11,13-bis(methylamino)-2,4,9-trioxatricyclo[8.4.0.0³,⁸]tetradecan-7-one
SMILES
[H][C@@]12O[C@H](C)CC(=O)[C@]1(O)O[C@]1([H])[C@@H](NC)[C@@H](O)[C@@H](NC)[C@H](O)[C@@]1([H])O2

Pharmacology

Indication

For use in the treatment of acute gonorrheal urethritis and proctitis in the male and acute gonorrheal cervicitis and proctitis in the female when due to susceptible strains of Neisseria gonorrhoeae.

Pharmacodynamics

Spectinomycin is an aminocyclitol antibiotic produced by a species of soil microorganism designated as Streptomyces spectabilis. In vitro studies have shown spectinomycin to be active against most strains of Neisseria gonorrhoeae (minimum inhibitory concentration <7.5 to 20 mcg/mL). Footprint studies indicate that spectinomycin exerts regional effects on ribosomal structure.

Mechanism of action

Spectinomycin is an inhibitor of protein synthesis in the bacterial cell; the site of action is the 30S ribosomal subunit. It is bactericidal in its action.

TargetActionsOrganism
A30S ribosomal protein S12
inhibitor
Escherichia coli (strain K12)
Absorption

Rapidly and almost completely absorbed after intramuscular injection.

Volume of distribution
Not Available
Protein binding

Not significant

Metabolism
Not Available
Route of elimination
Not Available
Half life

1 to 3 hours in patients with normal renal function and 10 to 30 hours in patients with impaired renal function with a creatinine clearance < 20 mL per minute.

Clearance
Not Available
Toxicity

Acute oral toxicity (LD50): >5000 mg/kg [Rat]. Information on overdosage in humans is not available.

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
PathwayCategory
Spectinomycin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Spectinomycin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Spectinomycin is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Spectinomycin is combined with 4-hydroxycoumarin.
AcenocoumarolThe risk or severity of bleeding can be increased when Spectinomycin is combined with Acenocoumarol.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Spectinomycin.
Anthrax immune globulin humanThe therapeutic efficacy of Anthrax immune globulin human can be decreased when used in combination with Spectinomycin.
Anthrax vaccineThe therapeutic efficacy of Anthrax vaccine can be decreased when used in combination with Spectinomycin.
Bacillus calmette-guerin substrain connaught live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain connaught live antigen can be decreased when used in combination with Spectinomycin.
Bacillus calmette-guerin substrain danish 1331 live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain danish 1331 live antigen can be decreased when used in combination with Spectinomycin.
Bacillus calmette-guerin substrain tice live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain tice live antigen can be decreased when used in combination with Spectinomycin.
Food Interactions
Not Available

References

Synthesis Reference

David R. White, "Intermediate compounds in the preparation of spectinomycin." U.S. Patent US4344882, issued August, 1966.

US4344882
General References
Not Available
External Links
Human Metabolome Database
HMDB0015055
KEGG Compound
C02078
PubChem Compound
15541
PubChem Substance
46505032
ChemSpider
14785
ChEBI
9215
ChEMBL
CHEMBL1167
Therapeutic Targets Database
DAP000403
PharmGKB
PA164781342
HET
SCM
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Spectinomycin
ATC Codes
J01XX04 — Spectinomycin
PDB Entries
1fjg / 4v56 / 4v57
MSDS
Download (24.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
Not AvailableCompletedTreatmentEpidural Analgesia / Labour1

Pharmacoeconomics

Manufacturers
  • Pharmacia and upjohn co
Packagers
  • Pfizer Inc.
  • Pharmacia Inc.
Dosage forms
FormRouteStrength
Kit400 mg/1mL
Powder, for solutionIntramuscular400 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityEasily soluble in cold waterNot Available
logP-2.3Not Available
pKa6.95MERCK INDEX (1996); pKa1
Predicted Properties
PropertyValueSource
Water Solubility150.0 mg/mLALOGPS
logP-1.4ALOGPS
logP-2.4ChemAxon
logS-0.35ALOGPS
pKa (Strongest Acidic)8.58ChemAxon
pKa (Strongest Basic)9.4ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area129.51 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity75.44 m3·mol-1ChemAxon
Polarizability33.39 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.7118
Blood Brain Barrier-0.9892
Caco-2 permeable-0.6803
P-glycoprotein substrateNon-substrate0.526
P-glycoprotein inhibitor INon-inhibitor0.6468
P-glycoprotein inhibitor IINon-inhibitor0.9228
Renal organic cation transporterNon-inhibitor0.9646
CYP450 2C9 substrateNon-substrate0.7711
CYP450 2D6 substrateNon-substrate0.8496
CYP450 3A4 substrateNon-substrate0.5056
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9182
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8434
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9254
Ames testNon AMES toxic0.7167
CarcinogenicityNon-carcinogens0.9602
BiodegradationNot ready biodegradable0.983
Rat acute toxicity1.8538 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.996
hERG inhibition (predictor II)Non-inhibitor0.9493
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-08fr-0981000000-7b067e918b209eac92b8
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-0009000000-b9eac7fc0b26b25322e5
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-0109000000-579b95f7f98de34557b5
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-1905000000-2a7f6f7210597e02ca8b
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0005-8900000000-cbcc3a787f8ddb194a17
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00dj-9200000000-8e0fffdf1e10bf82d5f6
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-000i-0931000000-72bf96c01e6ac30e14de
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-000i-0963000000-2806611756fc50c1eada

Taxonomy

Description
This compound belongs to the class of organic compounds known as 1,4-dioxanes. These are organic compounds containing 1,4-dioxane, an aliphatic six-member ring with two oxygen atoms in ring positions 1 and 4.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Dioxanes
Sub Class
1,4-dioxanes
Direct Parent
1,4-dioxanes
Alternative Parents
Oxanes / Secondary alcohols / Ketones / Hemiacetals / Cyclic alcohols and derivatives / 1,2-aminoalcohols / Polyols / Oxacyclic compounds / Dialkylamines / Acetals
show 3 more
Substituents
Para-dioxane / Oxane / Cyclic alcohol / 1,2-aminoalcohol / Secondary alcohol / Hemiacetal / Ketone / Acetal / Secondary aliphatic amine / Oxacycle
show 13 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
cyclic ketone, organic heterotricyclic compound, secondary amino compound, cyclic hemiketal, cyclic acetal (CHEBI:9215) / Actinamines (C02078)

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Trna binding
Specific Function
With S4 and S5 plays an important role in translational accuracy.Interacts with and stabilizes bases of the 16S rRNA that are involved in tRNA selection in the A site and with the mRNA backbone. Lo...
Gene Name
rpsL
Uniprot ID
P0A7S3
Uniprot Name
30S ribosomal protein S12
Molecular Weight
13736.995 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Yamagata H, Dombou M, Sato T, Mizushima S, Uchida H: Deletion mapping and heterogenote analysis of a mutation responsible for osmosis-sensitive growth, spectinomycin resistance, and alteration of cytoplasmic membrane in Escherichia coli. J Bacteriol. 1980 Aug;143(2):661-7. [PubMed:6451613]
  4. Gordeev VK, Turkov MI: [Functioning of amino acid operons in Escherichia coli strains with an altered transcription and translation apparatus. II. The effect of mutations in genes coding ribosomal protein S5 and translation elongation factor G on the functioning of the ilv operon]. Genetika. 1983;19(2):217-20. [PubMed:6339322]
  5. Eisenstein BI, Beachey EH, Ofek I: Influence of sublethal concentrations of antibiotics on the expression of the mannose-specific ligand of Escherichia coli. Infect Immun. 1980 Apr;28(1):154-9. [PubMed:6103875]
  6. Carter AP, Clemons WM, Brodersen DE, Morgan-Warren RJ, Wimberly BT, Ramakrishnan V: Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. Nature. 2000 Sep 21;407(6802):340-8. [PubMed:11014183]

Drug created on June 13, 2005 07:24 / Updated on November 13, 2018 08:11