Identification

Name
Streptomycin
Accession Number
DB01082  (APRD00412)
Type
Small Molecule
Groups
Approved, Vet approved
Description

Streptomycin is an aminoglycoside antibiotic produced by the soil actinomycete Streptomyces griseus. It acts by binding to the 30S ribosomal subunit of susceptible organisms and disrupting the initiation and elongation steps in protein synthesis. It is bactericidal due to effects that are not fully understood.

Structure
Thumb
Synonyms
  • 2,4-diguanidino-3,5,6-trihydroxycyclohexyl 5-deoxy-2-O-(2-deoxy-2-methylamino-alpha-L-glucopyranosyl)-3-C-formyl-beta-L-lyxopentanofuranoside
  • Estreptomicina
  • Streptomicina
  • Streptomycin
  • Streptomyzin
External IDs
NSC-14083
Product Ingredients
IngredientUNIICASInChI Key
Streptomycin SulfateCW25IKJ2023810-74-0CFCMMYICHMLDCC-QXQFOYBSSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Streptomycin for Injection USPPowder, for solution1 gIntramuscularSterimax Inc2001-10-15Not applicableCanada
Streptomycin Sulfate Injection USP 1g/2.5mlLiquid1 gIntramuscularPfizer1993-12-312000-07-26Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
StreptomycinInjection, powder, lyophilized, for solution1 g/1IntramuscularX Gen Pharmaceuticals, Inc.1998-06-30Not applicableUs
Streptomycin SulfateInjection, solution1 g/2.5mLIntramuscularRoerig1952-03-012001-09-01Us
Categories
UNII
Y45QSO73OB
CAS number
57-92-1
Weight
Average: 581.5741
Monoisotopic: 581.265669747
Chemical Formula
C21H39N7O12
InChI Key
UCSJYZPVAKXKNQ-HZYVHMACSA-N
InChI
InChI=1S/C21H39N7O12/c1-5-21(36,4-30)16(40-17-9(26-2)13(34)10(31)6(3-29)38-17)18(37-5)39-15-8(28-20(24)25)11(32)7(27-19(22)23)12(33)14(15)35/h4-18,26,29,31-36H,3H2,1-2H3,(H4,22,23,27)(H4,24,25,28)/t5-,6-,7+,8-,9-,10-,11+,12-,13-,14+,15+,16-,17-,18-,21+/m0/s1
IUPAC Name
1-[(1R,2R,3S,4R,5R,6S)-3-carbamimidamido-4-{[(2R,3R,4R,5S)-3-{[(2S,3S,4S,5R,6S)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy}-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy}-2,5,6-trihydroxycyclohexyl]guanidine
SMILES
CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@H]1[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](NC(N)=N)[C@@H](O)[C@@H]2NC(N)=N)O[C@@H](C)[C@]1(O)C=O

Pharmacology

Indication

For the treatment of tuberculosis. May also be used in combination with other drugs to treat tularemia (Francisella tularensis), plague (Yersia pestis), severe M. avium complex, brucellosis, and enterococcal endocarditis (e.g. E. faecalis, E. faecium).

Associated Conditions
Pharmacodynamics

Streptomycin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.

Mechanism of action

Aminoglycosides like Streptomycin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically Streptomycin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes.

TargetActionsOrganism
A30S ribosomal protein S12
inhibitor
Escherichia coli (strain K12)
A16S rRNA
inhibitor
Enteric bacteria and other eubacteria
UProtein-arginine deiminase type-4Not AvailableHuman
Absorption

Rapidly absorbed after intramuscular injection with peak serum concentrations attained after 1 - 2 hours. Not absorbed in the GI tract.

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

Small amounts are excreted in milk, saliva, and sweat. Streptomycin is excreted by glomerular filtration.

Half life

5 - 6 hours in adults with normal renal function

Clearance
Not Available
Toxicity

Nephrotoxic and ototoxic potential. Nephrotoxicity is caused by accumulation of the drug in proximal renal tubular cells, which results in cellular damage. Tubular cells may regenerate despite continued exposure and nephrotoxicity is usually mild and reversible. Streptomycin is the least nephrotoxic of the aminoglycosides owing to the small number of cationic amino groups in its structure. Otoxocity occurs via drug accumulation in the endolymph and perilymph of the inner ear. Accumulation causes irreversible damage to hair cells of the cochlea or summit of the ampullar cristae of the vestibular complex. High frequency hearing loss precedes low frequency hearing loss. Further toxicity may result in retrograde degeneration of the auditory nerve. Vestibular toxicity may result in vertigo, nausea and vomiting, dizziness and loss of balance. LD50=430 mg/kg (Orally in rats with Streptomycin Sulfate); Side effects include nausea, vomiting, and vertigo, paresthesia of face, rash, fever, urticaria, angioneurotic edema, and eosinophilia.

Affected organisms
  • Enteric bacteria and other eubacteria
  • Mycobacteria
  • Mycobacterium tuberculosis
  • Yersinia pestis
  • Francisella tularensis
  • Staphylococcus aureus
  • Enterococcus faecalis
Pathways
PathwayCategory
Streptomycin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Streptomycin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Streptomycin is combined with (S)-Warfarin.
1,10-PhenanthrolineThe therapeutic efficacy of 1,10-Phenanthroline can be decreased when used in combination with Streptomycin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Streptomycin is combined with 4-hydroxycoumarin.
AbacavirStreptomycin may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseStreptomycin may decrease the excretion rate of Acarbose which could result in a higher serum level.
AceclofenacThe risk or severity of nephrotoxicity can be increased when Aceclofenac is combined with Streptomycin.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Acemetacin is combined with Streptomycin.
AcenocoumarolThe risk or severity of bleeding can be increased when Streptomycin is combined with Acenocoumarol.
AcetaminophenStreptomycin may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Food Interactions
Not Available

References

Synthesis Reference

Arnold L. Demain, Kozo Nagaoka, "Derivatives of streptomycin and method of producing streptomycin derivatives by mutational biosynthesis." U.S. Patent US3993544, issued November 23, 1976.

US3993544
General References
Not Available
External Links
Human Metabolome Database
HMDB0015214
KEGG Compound
C00413
PubChem Compound
19649
PubChem Substance
46506845
ChemSpider
18508
BindingDB
50103513
ChEBI
17076
ChEMBL
CHEMBL372795
Therapeutic Targets Database
DAP000144
PharmGKB
PA451512
HET
SRY
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Streptomycin
ATC Codes
J01GA01 — StreptomycinJ04AM01 — Streptomycin and isoniazidA07AA54 — Streptomycin, combinationsA07AA04 — Streptomycin
AHFS Codes
  • 08:12.02 — Aminoglycosides
PDB Entries
1fjg / 1nta / 1ntb / 3hav / 4dr3 / 4dr5 / 4dr6 / 4dr7 / 4duz / 4dv1
show 10 more
MSDS
Download (73.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
2CompletedTreatmentInfection, Mycobacterium Avium-Intracellulare1
2, 3Active Not RecruitingTreatmentMycobacterium Ulcerans Infection1
2, 3CompletedTreatmentPlague1
3RecruitingTreatmentMulti-Drug Resistant Tuberculosis1
Not AvailableCompletedNot AvailablePatients Colonized by Klebsiella Pneumoniae1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis Infection1
Not AvailableCompletedTreatmentPulmonary Tuberculosis (TB)1
Not AvailableRecruitingNot AvailableTuberculosis Infection1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Ben Venue Laboratories Inc.
  • Gallipot
  • Sanofi-Aventis Inc.
  • X-Gen Pharmaceuticals
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntramuscular1 g/1
Powder, for solutionIntramuscular1 g
Injection, solutionIntramuscular1 g/2.5mL
LiquidIntramuscular1 g
Prices
Unit descriptionCostUnit
Streptomycin sulf 1 gm vial14.65USD vial
Streptomycin sulfate powder0.82USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP-6.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility12.8 mg/mLALOGPS
logP-2.6ALOGPS
logP-7.7ChemAxon
logS-1.7ALOGPS
pKa (Strongest Acidic)10.88ChemAxon
pKa (Strongest Basic)11.9ChemAxon
Physiological Charge3ChemAxon
Hydrogen Acceptor Count19ChemAxon
Hydrogen Donor Count14ChemAxon
Polar Surface Area331.43 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity149.47 m3·mol-1ChemAxon
Polarizability55.76 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8824
Blood Brain Barrier-0.9712
Caco-2 permeable-0.6968
P-glycoprotein substrateSubstrate0.5531
P-glycoprotein inhibitor INon-inhibitor0.7577
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.7782
CYP450 2C9 substrateNon-substrate0.7053
CYP450 2D6 substrateNon-substrate0.8177
CYP450 3A4 substrateNon-substrate0.5275
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9072
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8867
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8818
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.9528
BiodegradationNot ready biodegradable0.9821
Rat acute toxicity1.8409 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9924
hERG inhibition (predictor II)Non-inhibitor0.9009
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 - DI-ESI-Ion Trap , PositiveLC-MS/MSNot Available
MS/MS Spectrum - DI-ESI-Hybrid FT , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-001i-0000090000-37fcf4def2f5e472aa90
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-03di-0091010000-39300aec20bda5d23649
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-03di-0090000000-34b8374e2a80e4cb95ec
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-03xr-1090000000-0d28a95c3d70165872c6
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-014j-5190000000-87daef600d1a1a4b52d8
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-0200090000-e3f4de9e437da47f8b50
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-01q9-0911281000-307d692fcab3f0a93c0a
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03e9-0900250000-1e9e471e29850e7a3023
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-0660090000-e0be715ff2ef7bceed6e
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0udi-0090000000-da49dca8f3e875260220
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-0090000000-51b8b9878643820d5652
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0729-6940300000-cbd7d78f026f93380976
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00dj-9750000000-ea4bfbc8bf26152232f7
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00dj-9100000000-e44f835436ca5aa376a5
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0usi-9040000000-4cb87273cf38a98ccf69
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0000090000-f0c24196329215da6048
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001i-0000090000-0de059c38cbd52e00cce
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-01q9-0182190000-46e9dfef9871c913947b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03dj-1391000000-ae846bc34742e8a119c8
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0fdt-4790000000-c949fbfe981dc5f039e8

Taxonomy

Description
This compound belongs to the class of organic compounds known as aminocyclitol glycosides. These are organic compounds containing an amicocyclitol moiety glycosidically linked to a carbohydrate moiety. There are two major classes of aminoglycosides containing a 2-streptamine core. They are called 4,5- and 4,6-disubstituted 2-deoxystreptamines.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Aminocyclitol glycosides
Alternative Parents
O-glycosyl compounds / Cyclohexanols / Cyclitols and derivatives / Monosaccharides / Oxanes / Tetrahydrofurans / Tertiary alcohols / Guanidines / 1,2-aminoalcohols / Oxacyclic compounds
show 10 more
Substituents
Amino cyclitol glycoside / Glycosyl compound / O-glycosyl compound / Cyclohexanol / Monosaccharide / Cyclitol or derivatives / Oxane / Cyclic alcohol / Tertiary alcohol / Tetrahydrofuran
show 23 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
antibiotic antifungal drug, antibiotic fungicide, streptomycins (CHEBI:17076) / Streptidines, Antibiotic fungicides (C00413)

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. Mieskes KT, Rusch-Gerdes S, Truffot-Pernot C, Feldmann K, Tortoli E, Casal M, Loscher T, Rinder H: Rapid, simple, and culture-independent detection of rpsL codon 43 mutations that are highly predictive of streptomycin resistance in Mycobacterium tuberculosis. Am J Trop Med Hyg. 2000 Jul-Aug;63(1-2):56-60. [PubMed:11357996]
  2. Kenney TJ, Churchward G: Cloning and sequence analysis of the rpsL and rpsG genes of Mycobacterium smegmatis and characterization of mutations causing resistance to streptomycin. J Bacteriol. 1994 Oct;176(19):6153-6. [PubMed:7928982]
  3. Fukuda M, Koga H, Ohno H, Ogawa K, Yang B, Miyamoto J, Tomono K, Kohno S: [Relationship between streptomycin susceptibility and rpsL mutations of Mycobacterium tuberculosis strains]. Kekkaku. 1997 Sep;72(9):507-13. [PubMed:9364810]
2. 16S rRNA
Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
Yes
Actions
Inhibitor
References
  1. Okamoto S, Tamaru A, Nakajima C, Nishimura K, Tanaka Y, Tokuyama S, Suzuki Y, Ochi K: Loss of a conserved 7-methylguanosine modification in 16S rRNA confers low-level streptomycin resistance in bacteria. Mol Microbiol. 2007 Feb;63(4):1096-106. [PubMed:17238915]
  2. Nishimura K, Hosaka T, Tokuyama S, Okamoto S, Ochi K: Mutations in rsmG, encoding a 16S rRNA methyltransferase, result in low-level streptomycin resistance and antibiotic overproduction in Streptomyces coelicolor A3(2). J Bacteriol. 2007 May;189(10):3876-83. Epub 2007 Mar 23. [PubMed:17384192]
  3. Vila-Sanjurjo A, Lu Y, Aragonez JL, Starkweather RE, Sasikumar M, O'Connor M: Modulation of 16S rRNA function by ribosomal protein S12. Biochim Biophys Acta. 2007 Jul-Aug;1769(7-8):462-71. Epub 2007 Apr 20. [PubMed:17512991]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein-arginine deiminase activity
Specific Function
Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance. Citrullinates histone...
Gene Name
PADI4
Uniprot ID
Q9UM07
Uniprot Name
Protein-arginine deiminase type-4
Molecular Weight
74078.65 Da
References
  1. Knuckley B, Luo Y, Thompson PR: Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors. Bioorg Med Chem. 2008 Jan 15;16(2):739-45. Epub 2007 Oct 13. [PubMed:17964793]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. [PubMed:10411577]

Drug created on June 13, 2005 07:24 / Updated on December 16, 2018 03:11