Streptomycin

Identification

Summary

Streptomycin is an aminoglycoside antibiotic indicated to treat multi-drug resistant mycobacterium tuberculosis and various non-tuberculosis infections.

Generic Name
Streptomycin
DrugBank Accession Number
DB01082
Background

Streptomycin, an antibiotic derived from Streptomyces griseus, was the first aminoglycoside to be discovered and used in practice in the 1940s.3,5 Selman Waksman and eventually Albert Schatz were recognized with the Nobel Prize in Medicine for their discovery of streptomycin and its antibacterial activity.3,6 Although streptomycin was the first antibiotic determined to be effective against mycobacterium tuberculosis, it has fallen out of favor due to resistance and is now primarily used as adjunctive treatment in cases of multi-drug resistant tuberculosis.3

Type
Small Molecule
Groups
Approved, Vet approved
Structure
Thumb
Weight
Average: 581.5741
Monoisotopic: 581.265669747
Chemical Formula
C21H39N7O12
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

Pharmacology

Indication

Although streptomycin was the first antibiotic available for the treatment of mycobacterium tuberculosis, it is now largely a second line option due to resistance and toxicity.2 Streptomycin may also be used to treat a variety of other infections caused by susceptible strains of aerobic bacteria where other less toxic agents are ineffective. Examples include: Yersinia pestis, Francisella tularensis, Brucella, Calymmatobacterium granulomatis (donovanosis, granuloma inguinale), H. ducreyi (chancroid), H. influenzae (in respiratory, endocardial, and meningeal infections - concomitantly with another antibacterial agents). K. pneumoniae pneumonia (concomitantly with another antibacterial agent), E.coli, Proteus, A.aerogenes, K. pneumoniae, and Enterococcus faecalis in urinary tract infections, Streptococcus viridans, Enterococcus faecalis (in endocardial infections - concomitantly with penicillin), and Gram-negative bacillary bacteremia (concomitantly with another antibacterial agent).

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Although streptomycin originally had broad gram-negative and gram-positive coverage, its spectrum of activity has been significantly narrowed due to antibiotic resistance.2 Streptomycins current spectrum of activity includes susceptible strains of Yersinia pestis, Francisella tularensis, Brucella, Calymmatobacterium granulomatis, H. ducreyi, H. influenza, K. pneumoniae pneumonia, E.coli, Proteus, A. aerogenes, K. pneumoniae, Enterococcus faecalis, Streptococcus viridans, Enterococcus faecalis, and Gram-negative bacillary bacteremia. Streptomycin is not reliably active against pseudomonas aeruginosa.2

Similar to other aminoglycosides, streptomycin is considered to have a narrow therapeutic index.18 Characteristic toxicities of streptomycin include nephrotoxicity and ototoxicity.2,6 Patients should be carefully monitored for early signs of hearing loss and vestibular dysfunction in order to prevent permanent damage to sensorineural cells. Neuromuscular blockade has also been rarely reported.6

Mechanism of action

There are 3 key phases of aminoglycoside entry into cells.6 The first “ionic binding phase” occurs when polycationic aminoglycosides bind electrostatically to negatively charged components of bacterial cell membranes including with lipopolysaccharides and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acids and phospholipids within the cell membrane of Gram-positive bacteria. This binding results in displacement of divalent cations and increased membrane permeability, allowing for aminoglycoside entry.6,8,9,10

The second “energy-dependent phase I” of aminoglycoside entry into the cytoplasm relies on the proton-motive force and allows a limited amount of aminoglycoside access to its primary intracellular target - the bacterial 30S ribosome.6,10 This ultimately results in the mistranslation of proteins and disruption of the cytoplasmic membrane.2 Finally, in the “energy-dependent phase II” stage, concentration-dependent bacterial killing is observed. Aminoglycoside rapidly accumulates in the cell due to the damaged cytoplasmic membrane, and protein mistranslation and synthesis inhibition is amplified.6,10,11

Hence, aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modeling support this two-mechanism model.6,12

Inhibition of protein synthesis is a key component of aminoglycoside efficacy. Structural and cell biological studies suggest that aminoglycosides bind to the 16S rRNA in helix 44 (h44), near the A site of the 30S ribosomal subunit, altering interactions between h44 and h45. This binding also displaces two important residues, A1492 and A1493, from h44, mimicking normal conformational changes that occur with successful codon-anticodon pairing in the A site.13,14 Overall, aminoglycoside binding has several negative effects including inhibition of translation, initiation, elongation, and ribosome recycling.6,15,16 Recent evidence suggests that the latter effect is due to a cryptic second binding site situated in h69 of the 23S rRNA of the 50S ribosomal subunit.14,16 Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation.17 Mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above.6,11

TargetActionsOrganism
A16S ribosomal RNA
inhibitor
Enteric bacteria and other eubacteria
A23S ribosomal RNA
inhibitor
Enteric bacteria and other eubacteria
A30S ribosomal protein S12
inhibitor
Escherichia coli (strain K12)
ACytoplasmic membrane
incorporation into and destabilization
Bacteria
ABacterial outer membrane
incorporation into and destabilization
Bacteria
NProtein-arginine deiminase type-4
inhibitor
Humans
Absorption

Due to poor oral absorption, aminoglycosides including streptomycin are administered parenterally. Streptomycin is available as an intramuscular injection, and in some cases may be administered intravenously.2,3 A peak serum concentration of 25-50 mcg/mL is achieved within 1 hour after intramuscular administration of 1 gram of streptomycin.20

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Approximately 50% of streptomycin is eliminated in the urine within 24 hours after intravenous or intramuscular administration.7

Half-life

Streptomycins serum half-life is estimated to be 2.5 hours.2

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

The most common symptoms of streptomycin overdose are ototoxicity and vestibular impairment.2 Streptomycin is also associated with nephrotoxicity which presents as mild elevations in blood urea, mild proteinuria, and excess cellular excretion. While in severe cases, streptomycin may lead to permanent hearing loss and vestibular dysfunction, any associated nephrotoxicity is typically transient.2,4 In cases of toxicity, streptomycin serum concentrations may be lowered with dialysis.2

Pathways
PathwayCategory
Streptomycin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Streptomycin which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Streptomycin which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Streptomycin which could result in a higher serum level.
AcenocoumarolThe risk or severity of bleeding can be increased when Streptomycin is combined with Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Streptomycin which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Streptomycin which could result in a lower serum level and potentially a reduction in efficacy.
AcetylcholineThe therapeutic efficacy of Acetylcholine can be decreased when used in combination with Streptomycin.
AcetyldigitoxinThe risk or severity of adverse effects can be increased when Streptomycin is combined with Acetyldigitoxin.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Streptomycin which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Streptomycin which could result in a higher serum level.
Interactions
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Streptomycin SulfateCW25IKJ2023810-74-0CFCMMYICHMLDCC-QXQFOYBSSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Streptomycin for Injection USPPowder, for solution1 g / vialIntramuscularSterimax Inc2001-10-15Not applicableCanada flag
Streptomycin Sulfate Injection USP 1g/2.5mlLiquid1 g / 2.5 mLIntramuscularPfizer Canada Ulc1993-12-312000-07-26Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
StreptomycinInjection, powder, lyophilized, for solution1 g/1IntramuscularX-GEN Pharmaceuticals, Inc.1998-06-30Not applicableUS flag
Streptomycin SulfateInjection, solution1 g/2.5mLIntramuscularRoerig1952-03-012001-09-01US flag

Categories

ATC Codes
J04AM01 — Streptomycin and isoniazidJ01GA01 — StreptomycinA07AA54 — Streptomycin, combinationsA07AA04 — Streptomycin
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
1,2-aminoalcohol / Acetal / Alcohol / Aldehyde / Aliphatic heteromonocyclic compound / Amine / Amino cyclitol glycoside / Carbonyl group / Carboximidamide / Cyclic alcohol
show 23 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
antibiotic antifungal drug, antibiotic fungicide, streptomycins (CHEBI:17076) / Streptidines, Antibiotic fungicides (C00413)
Affected organisms
  • Enteric bacteria and other eubacteria
  • Mycobacteria
  • Mycobacterium tuberculosis
  • Yersinia pestis
  • Francisella tularensis
  • Staphylococcus aureus
  • Enterococcus faecalis

Chemical Identifiers

UNII
Y45QSO73OB
CAS number
57-92-1
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
N-[(1S,2R,3R,4S,5R,6R)-3-carbamimidamido-6-{[(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}-2,4,5-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

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
  1. Block M, Blanchard DL: Aminoglycosides . [Article]
  2. Waters M, Tadi P: Streptomycin . [Article]
  3. Authors unspecified: Aminoglycosides . [Article]
  4. Adeyemo AA, Oluwatosin O, Omotade OO: Study of streptomycin-induced ototoxicity: protocol for a longitudinal study. Springerplus. 2016 Jun 17;5(1):758. doi: 10.1186/s40064-016-2429-5. eCollection 2016. [Article]
  5. Laurell G: Pharmacological intervention in the field of ototoxicity. HNO. 2019 Jun;67(6):434-439. doi: 10.1007/s00106-019-0663-1. [Article]
  6. Serio AW, Keepers T, Andrews L, Krause KM: Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation. EcoSal Plus. 2018 Nov;8(1). doi: 10.1128/ecosalplus.ESP-0002-2018. [Article]
  7. Buggs CW, Pilling MA, Bronstein B, Hirshfeld JW, Worzniak L, Key LJ: THE ABSORPTION, DISTRIBUTION, AND EXCRETION OF STREPTOMYCIN IN MAN. J Clin Invest. 1946 Jan;25(1):94-102. doi: 10.1172/JCI101693. [Article]
  8. Moore RA, Bates NC, Hancock RE: Interaction of polycationic antibiotics with Pseudomonas aeruginosa lipopolysaccharide and lipid A studied by using dansyl-polymyxin. Antimicrob Agents Chemother. 1986 Mar;29(3):496-500. doi: 10.1128/aac.29.3.496. [Article]
  9. Hancock RE, Raffle VJ, Nicas TI: Involvement of the outer membrane in gentamicin and streptomycin uptake and killing in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1981 May;19(5):777-85. doi: 10.1128/aac.19.5.777. [Article]
  10. Taber HW, Mueller JP, Miller PF, Arrow AS: Bacterial uptake of aminoglycoside antibiotics. Microbiol Rev. 1987 Dec;51(4):439-57. [Article]
  11. Davis BD, Chen LL, Tai PC: Misread protein creates membrane channels: an essential step in the bactericidal action of aminoglycosides. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6164-8. doi: 10.1073/pnas.83.16.6164. [Article]
  12. Bulitta JB, Ly NS, Landersdorfer CB, Wanigaratne NA, Velkov T, Yadav R, Oliver A, Martin L, Shin BS, Forrest A, Tsuji BT: Two mechanisms of killing of Pseudomonas aeruginosa by tobramycin assessed at multiple inocula via mechanism-based modeling. Antimicrob Agents Chemother. 2015 Apr;59(4):2315-27. doi: 10.1128/AAC.04099-14. Epub 2015 Feb 2. [Article]
  13. O'Sullivan ME, Poitevin F, Sierra RG, Gati C, Dao EH, Rao Y, Aksit F, Ciftci H, Corsepius N, Greenhouse R, Hayes B, Hunter MS, Liang M, McGurk A, Mbgam P, Obrinsky T, Pardo-Avila F, Seaberg MH, Cheng AG, Ricci AJ, DeMirci H: Aminoglycoside ribosome interactions reveal novel conformational states at ambient temperature. Nucleic Acids Res. 2018 Oct 12;46(18):9793-9804. doi: 10.1093/nar/gky693. [Article]
  14. Ying L, Zhu H, Shoji S, Fredrick K: Roles of specific aminoglycoside-ribosome interactions in the inhibition of translation. RNA. 2019 Feb;25(2):247-254. doi: 10.1261/rna.068460.118. Epub 2018 Nov 9. [Article]
  15. Wallace BJ, Tai PC, Herzog EL, Davis BD: Partial inhibition of polysomal ribosomes of Escherichia coli by streptomycin. Proc Natl Acad Sci U S A. 1973 Apr;70(4):1234-7. doi: 10.1073/pnas.70.4.1234. [Article]
  16. Borovinskaya MA, Pai RD, Zhang W, Schuwirth BS, Holton JM, Hirokawa G, Kaji H, Kaji A, Cate JH: Structural basis for aminoglycoside inhibition of bacterial ribosome recycling. Nat Struct Mol Biol. 2007 Aug;14(8):727-32. doi: 10.1038/nsmb1271. Epub 2007 Jul 29. [Article]
  17. Tai PC, Wallace BJ, Davis BD: Streptomycin causes misreading of natural messenger by interacting with ribosomes after initiation. Proc Natl Acad Sci U S A. 1978 Jan;75(1):275-9. doi: 10.1073/pnas.75.1.275. [Article]
  18. Germovsek E, Barker CI, Sharland M: What do I need to know about aminoglycoside antibiotics? Arch Dis Child Educ Pract Ed. 2017 Apr;102(2):89-93. doi: 10.1136/archdischild-2015-309069. Epub 2016 Aug 9. [Article]
  19. Streptomycin FDA Label [Link]
  20. DailyMed Drug Label Information: Streptomycin injection [Link]
Human Metabolome Database
HMDB0015214
KEGG Compound
C00413
PubChem Compound
19649
PubChem Substance
46506845
ChemSpider
18508
BindingDB
50103513
RxNav
10109
ChEBI
17076
ChEMBL
CHEMBL372795
ZINC
ZINC000008214681
Therapeutic Targets Database
DAP000144
PharmGKB
PA451512
PDBe Ligand
SRY
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Streptomycin
PDB Entries
1fjg / 1nta / 1ntb / 3hav / 4dr3 / 4dr5 / 4dr6 / 4dr7 / 4duz / 4dv1
show 13 more
MSDS
Download (73.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Unknown StatusTreatmentReinfection Pulmonary Tuberculosis1
3RecruitingTreatmentPlague, Bubonic / Pneumonic Plague1
2CompletedTreatmentInfection, Mycobacterium Avium-Intracellulare1
2, 3CompletedTreatmentMycobacterium Ulcerans Infection1
2, 3CompletedTreatmentPlague1
1CompletedTreatmentHealthy Subjects (HS)1
1, 2CompletedTreatmentFrailty1
0TerminatedTreatmentOsteomyelitis1
Not AvailableCompletedNot AvailableColorectal Carcinoma (CRC) / Surgical Site Infections1
Not AvailableCompletedNot AvailablePatients Colonized by Klebsiella Pneumoniae1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Ben Venue Laboratories Inc.
  • Gallipot
  • Sanofi-Aventis Inc.
  • X-Gen Pharmaceuticals
Dosage Forms
FormRouteStrength
Injection, solutionIntramuscular1 g
Injection, powder, lyophilized, for solutionIntramuscular1 g/1
Powder, for solutionIntramuscular1 g / vial
Injection
Injection, solutionIntramuscular1 g/2.5mL
Injection, powder, for solutionIntramuscular1 g/vial
LiquidIntramuscular1 g / 2.5 mL
Injection, powder, for solutionIntramuscular
Injection, solutionIntramuscular
Syrup
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
boiling point (°C)872.9∓75.0°C at 760 mmHghttp://www.chemspider.com/Chemical-Structure.18508.html
logP-2.53http://www.chemspider.com/Chemical-Structure.18508.html
Predicted Properties
PropertyValueSource
Water Solubility12.8 mg/mLALOGPS
logP-2.6ALOGPS
logP-7.6ChemAxon
logS-1.7ALOGPS
pKa (Strongest Acidic)11.09ChemAxon
pKa (Strongest Basic)11.6ChemAxon
Physiological Charge3ChemAxon
Hydrogen Acceptor Count19ChemAxon
Hydrogen Donor Count14ChemAxon
Polar Surface Area331.43 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity149.47 m3·mol-1ChemAxon
Polarizability55.87 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

Targets

Drugtargets2
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Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Note: The above was chosen as a representative target protein in a representative bacterium, and does not encompass all proteins/bacteria affected by this agent.
In prokaryotes, the 16S rRNA is essential for recognizing the 5' end of mRNA and hence positioning it correctly on the ribosome. The 16S rRNA has a characteristic secondary structure in which half of the nucleotides are base-paired. The 16S rRNA sequence has been highly conserved and is often used for evolutionary and species comparative analysis.
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. [Article]
  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. [Article]
  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. [Article]
  4. Waters M, Tadi P: Streptomycin . [Article]
  5. Block M, Blanchard DL: Aminoglycosides . [Article]
Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Note: The above was chosen as a representative target protein in a representative bacterium, and does not encompass all proteins/bacteria affected by this agent.
In prokaryotes, the 23S rRNA is part of the large subunit (the 50S) that joins with the 30S small subunit to create the functional 70S ribosome. The ribosome is comprised of 3 RNAs: the 23S, the 16S and the 5S ribosomal RNAs. The 23S and the 5S associate with their respective proteins to make up the large subunit of the ribosome, while the 16S RNA associates with its proteins to make up the small subunit.
References
  1. Ying L, Zhu H, Shoji S, Fredrick K: Roles of specific aminoglycoside-ribosome interactions in the inhibition of translation. RNA. 2019 Feb;25(2):247-254. doi: 10.1261/rna.068460.118. Epub 2018 Nov 9. [Article]
  2. Borovinskaya MA, Pai RD, Zhang W, Schuwirth BS, Holton JM, Hirokawa G, Kaji H, Kaji A, Cate JH: Structural basis for aminoglycoside inhibition of bacterial ribosome recycling. Nat Struct Mol Biol. 2007 Aug;14(8):727-32. doi: 10.1038/nsmb1271. Epub 2007 Jul 29. [Article]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Note: The above was chosen as a representative target protein in a representative bacterium, and does not encompass all proteins/bacteria affected by this agent.
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. [Article]
  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. [Article]
  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. [Article]
4. Cytoplasmic membrane
Kind
Group
Organism
Bacteria
Pharmacological action
Yes
Actions
Incorporation into and destabilization
References
  1. Serio AW, Keepers T, Andrews L, Krause KM: Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation. EcoSal Plus. 2018 Nov;8(1). doi: 10.1128/ecosalplus.ESP-0002-2018. [Article]
  2. Taber HW, Mueller JP, Miller PF, Arrow AS: Bacterial uptake of aminoglycoside antibiotics. Microbiol Rev. 1987 Dec;51(4):439-57. [Article]
  3. Davis BD, Chen LL, Tai PC: Misread protein creates membrane channels: an essential step in the bactericidal action of aminoglycosides. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6164-8. doi: 10.1073/pnas.83.16.6164. [Article]
5. Bacterial outer membrane
Kind
Group
Organism
Bacteria
Pharmacological action
Yes
Actions
Incorporation into and destabilization
References
  1. Serio AW, Keepers T, Andrews L, Krause KM: Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation. EcoSal Plus. 2018 Nov;8(1). doi: 10.1128/ecosalplus.ESP-0002-2018. [Article]
  2. Moore RA, Bates NC, Hancock RE: Interaction of polycationic antibiotics with Pseudomonas aeruginosa lipopolysaccharide and lipid A studied by using dansyl-polymyxin. Antimicrob Agents Chemother. 1986 Mar;29(3):496-500. doi: 10.1128/aac.29.3.496. [Article]
  3. Hancock RE, Raffle VJ, Nicas TI: Involvement of the outer membrane in gentamicin and streptomycin uptake and killing in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1981 May;19(5):777-85. doi: 10.1128/aac.19.5.777. [Article]
  4. Taber HW, Mueller JP, Miller PF, Arrow AS: Bacterial uptake of aminoglycoside antibiotics. Microbiol Rev. 1987 Dec;51(4):439-57. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
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. [Article]

Drug created on June 13, 2005 13:24 / Updated on October 26, 2021 21:40