Identification

Name
Paromomycin
Accession Number
DB01421
Type
Small Molecule
Groups
Approved, Investigational
Description

An oligosaccharide antibiotic produced by various streptomyces. [PubChem]

Structure
Thumb
Synonyms
  • (1R,2R,3S,4R,6S)-4,6-Diamino-2-{[3-O-(2,6-diamino-2,6-dideoxy-beta-L-idopyranosyl)-beta-D-ribofuranosyl]oxy}-3-hydroxycyclohexyl 2-amino-2-deoxy-alpha-D-glucopyranoside
  • Aminosidin
  • Aminosidine
  • Catenulin
  • Crestomycin
  • Estomycin
  • Hydroxymycin
  • Monomycin a
  • Neomycin e
  • Paromomicina
  • PAROMOMYCIN
  • Paromomycin i
  • Paromomycine
  • Paromomycinum
  • Paucimycin
  • Paucimycinum
  • Zygomycin a1
External IDs
ANTIBIOTIC 503-3 / ANTIBIOTIC SF 767B / R 400 / R-400
Product Ingredients
IngredientUNIICASInChI Key
Paromomycin sulfate845NU6GJPS1263-89-4LJRDOKAZOAKLDU-UDXJMMFXSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Humatin Cap 250mgCapsule250 mgOralErfa Canada 2012 Inc1994-12-31Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
HumatinCapsule250 mg/1OralMonarch Pharmaceuticals, Inc.1981-01-032008-11-11Us
Paromomycin SulfateCapsule250 mg/1OralSun Pharmaceutical Industries Limited1997-06-30Not applicableUs
Paromomycin SulfateCapsule250 mg/1OralCentral Texas Community Health Centers2009-10-22Not applicableUs
Paromomycin SulfateCapsule250 mg/1OralPhysicians Total Care, Inc.1997-10-012010-06-30Us
Paromomycin SulfateCapsule250 mg/1OralDepartment Of State Health Services, Pharmacy Branch2009-10-22Not applicableUs
Paromomycin SulfateCapsule, gelatin coated250 mg/1OralX Gen Pharmaceuticals, Inc.2007-12-172009-05-01Us
Paromomycin SulfateCapsule250 mg/1OralHeritage2009-10-22Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
HumatinParomomycin sulfate (250 mg/1)CapsuleOralPhysicians Total Care, Inc.1994-03-112011-05-31Us
International/Other Brands
Humatin (Parke Davis (now Pfizer))
Categories
UNII
61JJC8N5ZK
CAS number
7542-37-2
Weight
Average: 615.6285
Monoisotopic: 615.296301173
Chemical Formula
C23H45N5O14
InChI Key
UOZODPSAJZTQNH-LSWIJEOBSA-N
InChI
InChI=1S/C23H45N5O14/c24-2-7-13(32)15(34)10(27)21(37-7)41-19-9(4-30)39-23(17(19)36)42-20-12(31)5(25)1-6(26)18(20)40-22-11(28)16(35)14(33)8(3-29)38-22/h5-23,29-36H,1-4,24-28H2/t5-,6+,7+,8-,9-,10-,11-,12+,13-,14-,15-,16-,17-,18-,19-,20-,21-,22-,23+/m1/s1
IUPAC Name
(2S,3S,4R,5R,6R)-5-amino-2-(aminomethyl)-6-{[(2R,3S,4R,5S)-5-{[(1R,2R,3S,5R,6S)-3,5-diamino-2-{[(2S,3R,4R,5S,6R)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-6-hydroxycyclohexyl]oxy}-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxy}oxane-3,4-diol
SMILES
NC[C@@H]1O[C@H](O[C@@H]2[C@@H](CO)O[C@@H](O[C@@H]3[C@@H](O)[C@H](N)C[C@H](N)[C@H]3O[C@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3N)[C@@H]2O)[C@H](N)[C@@H](O)[C@@H]1O

Pharmacology

Indication

For the treatment of acute and chronic intestinal amebiasis (it is not effective in extraintestinal amebiasis). Also for the management of hepatic coma as adjunctive therapy.

Associated Conditions
Pharmacodynamics

Paromomycin is a broad spectrum aminoglycoside antibiotic produced by Streptomyces rimosus var. paromomycinus. The in vitro and in vivo antibacterial action of paromomycin closely parallels that of neomycin.

Mechanism of action

Paromomycin inhibits protein synthesis by binding to 16S ribosomal RNA. Bacterial proteins are synthesized by ribosomal RNA complexes which are composed of 2 subunits, a large subunit (50s) and small (30s) subunit, which forms a 70s ribosomal subunit. tRNA binds to the top of this ribosomal structure. Paramomycin binds to the A site, which causes defective polypeptide chains to be produced. Continuous production of defective proteins eventually leads to bacterial death.

TargetActionsOrganism
A30S ribosomal protein S10
inhibitor
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
A16S rRNA
inhibitor
Enteric bacteria and other eubacteria
Absorption

Poorly absorbed after oral administration, with almost 100% of the drug recoverable in the stool.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
PathwayCategory
Paromomycin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of 1,10-Phenanthroline can be decreased when used in combination with Paromomycin.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Paromomycin is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Paromomycin.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Paromomycin.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Paromomycin.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Paromomycin is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Paromomycin.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Paromomycin.
AceclofenacThe risk or severity of nephrotoxicity can be increased when Aceclofenac is combined with Paromomycin.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Acemetacin is combined with Paromomycin.
Food Interactions
  • Take with food.

References

Synthesis Reference

Federico Arcamone, Giuseppe Cassinelli, "Paromomycin derivatives and process for the preparation thereof." U.S. Patent US4021601, issued October, 1967.

US4021601
General References
  1. Vicens Q, Westhof E: Crystal structure of paromomycin docked into the eubacterial ribosomal decoding A site. Structure. 2001 Aug;9(8):647-58. [PubMed:11587639]
External Links
Human Metabolome Database
HMDB0015490
KEGG Compound
C00832
PubChem Compound
165580
PubChem Substance
46505391
ChemSpider
145115
ChEBI
7934
ChEMBL
CHEMBL370143
Therapeutic Targets Database
DAP000407
PharmGKB
PA164784023
HET
PAR
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Paromomycin_sulfate
ATC Codes
A07AA06 — Paromomycin
AHFS Codes
  • 08:30.04 — Amebicides
PDB Entries
1fjg / 1fyp / 1ibk / 1ibl / 1j7t / 1n32 / 1n33 / 1vvj / 1xmo / 1xmq
show 69 more

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
2CompletedTreatmentCryptosporidiosis infection / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentLeishmaniasis, Cutaneous4
2RecruitingTreatmentPKDL - Post-Kala-Azar Dermal Leishmanioid1
2TerminatedTreatmentLeishmaniasis, Cutaneous2
2, 3RecruitingTreatmentLeishmania Braziliensis Complex / Leishmaniasis, American / Leishmaniasis, Cutaneous / Leishmaniasis; American, Cutaneous1
3CompletedTreatmentLeishmaniasis, Cutaneous1
3CompletedTreatmentVisceral Leishmaniasis5
3RecruitingTreatmentVisceral Leishmaniasis1
4CompletedTreatmentVisceral Leishmaniasis1
Not AvailableAvailableNot AvailableLeishmaniasis, Cutaneous1
Not AvailableCompletedTreatmentTuberculosis, Pulmonary1
Not AvailableCompletedTreatmentVisceral Leishmaniasis1
Not AvailableTerminatedTreatmentCryptosporidiosis infection / Human Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Caraco Pharmaceutical Labs
  • Heritage Pharmaceuticals
  • Kaiser Foundation Hospital
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
CapsuleOral250 mg/1
CapsuleOral250 mg
Capsule, gelatin coatedOral250 mg/1
Prices
Unit descriptionCostUnit
Paromomycin 250 mg capsule5.67USD capsule
Humatin 250 mg capsule2.67USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility79.7 mg/mLALOGPS
logP-2.9ALOGPS
logP-8.3ChemAxon
logS-0.89ALOGPS
pKa (Strongest Acidic)12.23ChemAxon
pKa (Strongest Basic)9.94ChemAxon
Physiological Charge5ChemAxon
Hydrogen Acceptor Count19ChemAxon
Hydrogen Donor Count13ChemAxon
Polar Surface Area347.32 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity134.24 m3·mol-1ChemAxon
Polarizability60.4 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8617
Blood Brain Barrier-0.9659
Caco-2 permeable-0.7502
P-glycoprotein substrateNon-substrate0.5164
P-glycoprotein inhibitor INon-inhibitor0.8023
P-glycoprotein inhibitor IINon-inhibitor0.8764
Renal organic cation transporterNon-inhibitor0.7886
CYP450 2C9 substrateNon-substrate0.8231
CYP450 2D6 substrateNon-substrate0.8041
CYP450 3A4 substrateNon-substrate0.6473
CYP450 1A2 substrateNon-inhibitor0.9157
CYP450 2C9 inhibitorNon-inhibitor0.9147
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9034
CYP450 3A4 inhibitorNon-inhibitor0.9471
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8446
Ames testNon AMES toxic0.6934
CarcinogenicityNon-carcinogens0.9505
BiodegradationNot ready biodegradable0.8587
Rat acute toxicity1.4850 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9728
hERG inhibition (predictor II)Non-inhibitor0.81
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as 4,5-disubstituted 2-deoxystreptamines. These are 2-deoxystreptamine aminoglycosides that a glycosidically linked to a pyranose of furanose unit at the C4- and C5-positions.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
4,5-disubstituted 2-deoxystreptamines
Alternative Parents
O-glycosyl compounds / Disaccharides / Aminocyclitols and derivatives / Cyclohexylamines / Cyclohexanols / Oxanes / Tetrahydrofurans / 1,2-aminoalcohols / Oxacyclic compounds / Acetals
show 4 more
Substituents
4,5-disubstituted 2-deoxystreptamine / Disaccharide / Glycosyl compound / O-glycosyl compound / Aminocyclitol or derivatives / Cyclohexanol / Cyclohexylamine / Cyclitol or derivatives / Oxane / Tetrahydrofuran
show 16 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
aminoglycoside antibiotic, amino cyclitol glycoside (CHEBI:7934)

Targets

Kind
Protein
Organism
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Trna binding
Specific Function
Part of the top of the 30S subunit head.
Gene Name
rpsJ
Uniprot ID
Q5SHN7
Uniprot Name
30S ribosomal protein S10
Molecular Weight
11929.82 Da
References
  1. Dlugosz M, Trylska J: Aminoglycoside association pathways with the 30S ribosomal subunit. J Phys Chem B. 2009 May 21;113(20):7322-30. doi: 10.1021/jp8112914. [PubMed:19438282]
2. 16S rRNA
Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
Yes
Actions
Inhibitor
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. Konno T, Kurita D, Takahashi T, Muto A, Himeno H: Initiation-shift of trans-translation by aminoglycosides. Nucleic Acids Symp Ser (Oxf). 2004;(48):299-300. [PubMed:17150597]
  4. Chao PW, Chow CS: Monitoring aminoglycoside-induced conformational changes in 16S rRNA through acrylamide quenching. Bioorg Med Chem. 2007 Jun 1;15(11):3825-31. Epub 2007 Mar 13. [PubMed:17399988]

Drug created on July 24, 2007 04:03 / Updated on October 16, 2018 08:36