Josamycin

Identification

Name
Josamycin
Accession Number
DB01321
Type
Small Molecule
Groups
Approved
Description

A macrolide antibiotic from Streptomyces narbonensis. The drug has antimicrobial activity against a wide spectrum of pathogens. [PubChem]

Structure
Thumb
Synonyms
  • Antibiotic yl-704 a3
  • JM
  • Josamicina
  • Josamycine
  • Josamycinum
  • Kitasamycin a3
  • Leucomycin A3
  • Leucomycin v 3-acetate 4(b)-(3-methylbutanoate)
  • Leucomycin v 3-acetate 4(beta)-(3-methylbutanoate)
  • Leucomycin v 3-acetate 4b-(3-methylbutanoate)
  • Leucomycin V, 3-acetate 4(sup B)-(3-methylbutanoate)
  • Leucomycin V, 3-acetate 4(sup beta)-(3-methylbutanoate)
  • Leucomycin V, 3-acetate 4B-(3-methylbutanoate)
  • Turimycin a5
  • yl-704 a3
External IDs
Antibiotic yl-704 A3 / EN-141
Product Ingredients
Not Available
Approved Prescription Products
Not Available
Approved Generic Prescription Products
Not Available
Approved Over the Counter Products
Not Available
Unapproved/Other Products
Not Available
International/Other Brands
Josacine / Kitasamycin A3 / Turimycin A5
Brand mixtures
Not Available
Categories
UNII
HV13HFS217
CAS number
16846-24-5
Weight
Average: 827.995
Monoisotopic: 827.466720543
Chemical Formula
C42H69NO15
InChI Key
XJSFLOJWULLJQS-NGVXBBESSA-N
InChI
InChI=1S/C42H69NO15/c1-23(2)19-32(47)56-40-27(6)53-34(22-42(40,8)50)57-37-26(5)54-41(36(49)35(37)43(9)10)58-38-29(17-18-44)20-24(3)30(46)16-14-12-13-15-25(4)52-33(48)21-31(39(38)51-11)55-28(7)45/h12-14,16,18,23-27,29-31,34-41,46,49-50H,15,17,19-22H2,1-11H3/b13-12+,16-14+/t24-,25-,26-,27+,29+,30+,31-,34+,35-,36-,37-,38+,39+,40+,41+,42-/m1/s1
IUPAC Name
(2S,3S,4R,6S)-6-{[(2R,3S,4R,5R,6S)-6-{[(4R,5S,6S,7R,9R,10R,11E,13E,16R)-4-(acetyloxy)-10-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-7-(2-oxoethyl)-1-oxacyclohexadeca-11,13-dien-6-yl]oxy}-4-(dimethylamino)-5-hydroxy-2-methyloxan-3-yl]oxy}-4-hydroxy-2,4-dimethyloxan-3-yl 3-methylbutanoate
SMILES

Pharmacology

Indication

For the treatment of bacterial infections.

Structured Indications
Not Available
Pharmacodynamics

Josamycin is a macrolide antibiotic from Streptomyces narbonensis. The drug has antimicrobial activity against a wide spectrum of pathogens.

Mechanism of action

The mechanism of action of macrolides such as Josamycin is via inhibition of bacterial protein biosynthesis by binding reversibly to the subunit 50S of the bacterial ribosome, thereby inhibiting translocation of peptidyl tRNA. This action is mainly bacteriostatic, but can also be bactericidal in high concentrations. Macrolides tend to accumulate within leukocytes, and are therefore actually transported into the site of infection.

TargetActionsOrganism
A50S ribosomal protein L4
inhibitor
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Absorption
Not Available
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
Josamycin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Josamycin.Approved
AcetyldigitoxinThe serum concentration of Acetyldigitoxin can be increased when it is combined with Josamycin.Approved
AlfentanilThe serum concentration of Alfentanil can be increased when it is combined with Josamycin.Approved, Illicit
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Josamycin.Approved, Illicit, Investigational
Ambroxol acefyllinateThe metabolism of Ambroxol acefyllinate can be decreased when combined with Josamycin.Experimental
AminophyllineThe metabolism of Aminophylline can be decreased when combined with Josamycin.Approved
AmlodipineThe metabolism of Amlodipine can be decreased when combined with Josamycin.Approved
AmrinoneThe metabolism of Amrinone can be decreased when combined with Josamycin.Approved
AzelnidipineThe metabolism of Azelnidipine can be decreased when combined with Josamycin.Approved
AzimilideThe metabolism of Azimilide can be decreased when combined with Josamycin.Investigational
BarnidipineThe metabolism of Barnidipine can be decreased when combined with Josamycin.Approved
BCG vaccineThe therapeutic efficacy of Bcg can be decreased when used in combination with Josamycin.Investigational
BenidipineThe metabolism of Benidipine can be decreased when combined with Josamycin.Approved
BepridilThe metabolism of Bepridil can be decreased when combined with Josamycin.Approved, Withdrawn
BromocriptineThe serum concentration of Bromocriptine can be increased when it is combined with Josamycin.Approved, Investigational
BuspironeThe metabolism of Buspirone can be decreased when combined with Josamycin.Approved, Investigational
CabergolineThe serum concentration of Cabergoline can be increased when it is combined with Josamycin.Approved
CarbamazepineThe metabolism of Carbamazepine can be decreased when combined with Josamycin.Approved, Investigational
CarboxyamidotriazoleThe metabolism of Cai can be decreased when combined with Josamycin.Investigational
CilnidipineThe metabolism of Cilnidipine can be decreased when combined with Josamycin.Approved
CinnarizineThe metabolism of Cinnarizine can be decreased when combined with Josamycin.Approved
CisaprideThe metabolism of Cisapride can be decreased when combined with Josamycin.Approved, Investigational, Withdrawn
CyclosporineThe metabolism of Cyclosporine can be decreased when combined with Josamycin.Approved, Investigational, Vet Approved
DarodipineThe metabolism of Darodipine can be decreased when combined with Josamycin.Experimental
DeslanosideThe serum concentration of Deslanoside can be increased when it is combined with Josamycin.Approved
DicoumarolThe serum concentration of Dicoumarol can be increased when it is combined with Josamycin.Approved
DigitoxinThe serum concentration of Digitoxin can be increased when it is combined with Josamycin.Approved
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Josamycin.Approved
DihydroergotamineThe serum concentration of Dihydroergotamine can be increased when it is combined with Josamycin.Approved
DiltiazemThe metabolism of Diltiazem can be decreased when combined with Josamycin.Approved
DisopyramideJosamycin may increase the QTc-prolonging activities of Disopyramide.Approved
DotarizineThe metabolism of Dotarizine can be decreased when combined with Josamycin.Investigational
EfonidipineThe metabolism of Efonidipine can be decreased when combined with Josamycin.Approved
EperisoneThe metabolism of Eperisone can be decreased when combined with Josamycin.Approved, Investigational
Ergoloid mesylateThe serum concentration of Ergoloid mesylate can be increased when it is combined with Josamycin.Approved
ErgonovineThe serum concentration of Ergonovine can be increased when it is combined with Josamycin.Approved
ErgotamineThe serum concentration of Ergotamine can be increased when it is combined with Josamycin.Approved
EstazolamThe serum concentration of Estazolam can be increased when it is combined with Josamycin.Approved, Illicit
Ethyl biscoumacetateThe serum concentration of Ethyl biscoumacetate can be increased when it is combined with Josamycin.Withdrawn
FelodipineThe metabolism of Felodipine can be decreased when combined with Josamycin.Approved, Investigational
FendilineThe metabolism of Fendiline can be decreased when combined with Josamycin.Withdrawn
FluindioneThe serum concentration of Fluindione can be increased when it is combined with Josamycin.Investigational
FlunarizineThe metabolism of Flunarizine can be decreased when combined with Josamycin.Approved
GabapentinThe metabolism of Gabapentin can be decreased when combined with Josamycin.Approved, Investigational
GallopamilThe metabolism of Gallopamil can be decreased when combined with Josamycin.Investigational
IsradipineThe metabolism of Isradipine can be decreased when combined with Josamycin.Approved
LacidipineThe metabolism of Lacidipine can be decreased when combined with Josamycin.Approved
LamotrigineThe metabolism of Lamotrigine can be decreased when combined with Josamycin.Approved, Investigational
LercanidipineThe metabolism of Lercanidipine can be decreased when combined with Josamycin.Approved, Investigational
Magnesium SulfateThe metabolism of Magnesium Sulfate can be decreased when combined with Josamycin.Approved, Vet Approved
ManidipineThe metabolism of Manidipine can be decreased when combined with Josamycin.Approved
MibefradilThe metabolism of Mibefradil can be decreased when combined with Josamycin.Withdrawn
MidazolamThe serum concentration of Midazolam can be increased when it is combined with Josamycin.Approved, Illicit
NaftopidilThe metabolism of Naftopidil can be decreased when combined with Josamycin.Investigational
NicardipineThe metabolism of Nicardipine can be decreased when combined with Josamycin.Approved
NifedipineThe metabolism of Nifedipine can be decreased when combined with Josamycin.Approved
NiguldipineThe metabolism of Niguldipine can be decreased when combined with Josamycin.Experimental
NiludipineThe metabolism of Niludipine can be decreased when combined with Josamycin.Experimental
NilvadipineThe metabolism of Nilvadipine can be decreased when combined with Josamycin.Approved
NimesulideThe metabolism of Nimesulide can be decreased when combined with Josamycin.Approved, Withdrawn
NimodipineThe metabolism of Nimodipine can be decreased when combined with Josamycin.Approved
NisoldipineThe metabolism of Nisoldipine can be decreased when combined with Josamycin.Approved
NitrendipineThe metabolism of Nitrendipine can be decreased when combined with Josamycin.Approved
OleandrinThe serum concentration of Anvirzel can be increased when it is combined with Josamycin.Experimental
OuabainThe serum concentration of Ouabain can be increased when it is combined with Josamycin.Approved
PerhexilineThe metabolism of Perhexiline can be decreased when combined with Josamycin.Approved
PhenindioneThe serum concentration of Phenindione can be increased when it is combined with Josamycin.Approved
PhenprocoumonThe serum concentration of Phenprocoumon can be increased when it is combined with Josamycin.Approved
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Josamycin.Approved
PimozideJosamycin may increase the QTc-prolonging activities of Pimozide.Approved
PinaveriumThe metabolism of Pinaverium can be decreased when combined with Josamycin.Approved
PregabalinThe metabolism of Pregabalin can be decreased when combined with Josamycin.Approved, Illicit, Investigational
PrenylamineThe metabolism of Prenylamine can be decreased when combined with Josamycin.Withdrawn
QuinineThe serum concentration of Quinine can be increased when it is combined with Josamycin.Approved
RepaglinideThe serum concentration of Repaglinide can be increased when it is combined with Josamycin.Approved, Investigational
RifabutinThe metabolism of Rifabutin can be decreased when combined with Josamycin.Approved
RifampicinThe metabolism of Rifampicin can be decreased when combined with Josamycin.Approved
RilpivirineThe serum concentration of Rilpivirine can be increased when it is combined with Josamycin.Approved
RisedronateThe metabolism of Risedronate can be decreased when combined with Josamycin.Approved, Investigational
SirolimusThe metabolism of Sirolimus can be decreased when combined with Josamycin.Approved, Investigational
TacrolimusThe serum concentration of Tacrolimus can be increased when it is combined with Josamycin.Approved, Investigational
TemsirolimusThe risk or severity of adverse effects can be increased when Josamycin is combined with Temsirolimus.Approved
TerfenadineJosamycin may increase the QTc-prolonging activities of Terfenadine.Withdrawn
TheophyllineThe metabolism of Theophylline can be decreased when combined with Josamycin.Approved
Tolfenamic AcidThe metabolism of Tolfenamic Acid can be decreased when combined with Josamycin.Approved
TranilastThe metabolism of Tranilast can be decreased when combined with Josamycin.Approved, Investigational
TriazolamThe serum concentration of Triazolam can be increased when it is combined with Josamycin.Approved
VerapamilThe metabolism of Verapamil can be decreased when combined with Josamycin.Approved
VinblastineThe serum concentration of Vinblastine can be increased when it is combined with Josamycin.Approved
VincristineThe serum concentration of Vincristine can be increased when it is combined with Josamycin.Approved, Investigational
VindesineThe serum concentration of Vindesine can be increased when it is combined with Josamycin.Approved
VinorelbineThe serum concentration of Vinorelbine can be increased when it is combined with Josamycin.Approved, Investigational
VinpocetineThe metabolism of Vinpocetine can be decreased when combined with Josamycin.Investigational
WarfarinThe serum concentration of Warfarin can be increased when it is combined with Josamycin.Approved
XylometazolineThe metabolism of Xylometazoline can be decreased when combined with Josamycin.Approved
ZiconotideThe metabolism of Ziconotide can be decreased when combined with Josamycin.Approved
Food Interactions
Not Available

References

Synthesis Reference

Takashi Osono, Kiruko Moriyama, Keisuke Murakami, Hamao Umezawa, "Process for the production of monopropionyl-josamycin-2." U.S. Patent US4001399, issued January, 1972.

US4001399
General References
  1. Przybylski P, Pyta K, Stefanska J, Brzezinski B, Bartl F: Structure elucidation, complete NMR assignment and PM5 theoretical studies of new hydroxy-aminoalkyl-alpha,beta-unsaturated derivatives of the macrolide antibiotic josamycin. Magn Reson Chem. 2010 Apr;48(4):286-96. doi: 10.1002/mrc.2574. [PubMed:20186698 ]
External Links
Human Metabolome Database
HMDB15418
KEGG Drug
D01235
KEGG Compound
C12662
PubChem Compound
5282165
PubChem Substance
46505431
ChemSpider
4445361
ChEBI
31739
ChEMBL
CHEMBL224436
Therapeutic Targets Database
DAP000887
PharmGKB
PA164749133
Wikipedia
Josamycin
ATC Codes
J01FA07 — Josamycin
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentPremature Babies1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)131.5 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.0535 mg/mLALOGPS
logP3.47ALOGPS
logP3.22ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)12.67ChemAxon
pKa (Strongest Basic)7.9ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count13ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area206.05 Å2ChemAxon
Rotatable Bond Count14ChemAxon
Refractivity211.03 m3·mol-1ChemAxon
Polarizability87.91 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.5235
Blood Brain Barrier-0.9659
Caco-2 permeable-0.6872
P-glycoprotein substrateSubstrate0.586
P-glycoprotein inhibitor IInhibitor0.901
P-glycoprotein inhibitor IIInhibitor0.901
Renal organic cation transporterNon-inhibitor0.9274
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5659
CYP450 1A2 substrateNon-inhibitor0.907
CYP450 2C9 inhibitorNon-inhibitor0.917
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9118
CYP450 3A4 inhibitorNon-inhibitor0.8953
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9564
Ames testNon AMES toxic0.8389
CarcinogenicityNon-carcinogens0.9287
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.8513 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.978
hERG inhibition (predictor II)Non-inhibitor0.9424
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 LC-MS/MS Spectrum - 10V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 20V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 40V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 10V, NegativePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 20V, NegativePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 40V, NegativePredicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of chemical entities known as aminoglycosides. These are molecules or a portion of a molecule composed of amino-modified sugars.
Kingdom
Chemical entities
Super Class
Organic compounds
Class
Organic oxygen compounds
Sub Class
Organooxygen compounds
Direct Parent
Aminoglycosides
Alternative Parents
Macrolides and analogues / Disaccharides / O-glycosyl compounds / Tricarboxylic acids and derivatives / Fatty acid esters / Oxanes / Tertiary alcohols / Alpha-hydrogen aldehydes / 1,2-aminoalcohols / Secondary alcohols
show 10 more
Substituents
Aminoglycoside core / Macrolide / Disaccharide / Glycosyl compound / O-glycosyl compound / Tricarboxylic acid or derivatives / Fatty acid ester / Fatty acyl / Oxane / Alpha-hydrogen aldehyde
show 24 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
tertiary alcohol, tertiary amino compound, macrolide antibiotic, acetate ester, disaccharide derivative, glycoside, aldehyde (CHEBI:31739 )

Targets

Kind
Protein
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Structural constituent of ribosome
Specific Function
One of the primary rRNA binding proteins, this protein initially binds near the 5'-end of the 23S rRNA. It is important during the early stages of 50S assembly. It makes multiple contacts with diff...
Gene Name
rplD
Uniprot ID
P44345
Uniprot Name
50S ribosomal protein L4
Molecular Weight
21954.185 Da
References
  1. Tait-Kamradt A, Davies T, Cronan M, Jacobs MR, Appelbaum PC, Sutcliffe J: Mutations in 23S rRNA and ribosomal protein L4 account for resistance in pneumococcal strains selected in vitro by macrolide passage. Antimicrob Agents Chemother. 2000 Aug;44(8):2118-25. [PubMed:10898684 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Drug created on June 30, 2007 11:19 / Updated on September 01, 2017 10:38