Identification
NameJosamycin
Accession NumberDB01321
TypeSmall Molecule
GroupsApproved
DescriptionA macrolide antibiotic from Streptomyces narbonensis. The drug has antimicrobial activity against a wide spectrum of pathogens. [PubChem]
Structure
Thumb
Synonyms
Antibiotic yl-704 a3
EN-141
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
Product Ingredients Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
JosacineNot Available
Kitasamycin A3Not Available
Turimycin A5Not Available
Brand mixturesNot Available
Categories
UNIIHV13HFS217
CAS number16846-24-5
WeightAverage: 827.995
Monoisotopic: 827.466720543
Chemical FormulaC42H69NO15
InChI KeyXJSFLOJWULLJQS-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
CO[[email protected]]1[[email protected]](OC(=O)C)CC(=O)O[[email protected]](C)C\C=C\C=C\[[email protected]](O)[[email protected]](C)C[[email protected]](CC=O)[C@@H]1O[C@@H]1O[[email protected]](C)[C@@H](O[C@@H]2O[C@@H](C)[[email protected]](OC(=O)CC(C)C)[C@](C)(O)C2)[[email protected]](N(C)C)[[email protected]]1O
Pharmacology
IndicationFor the treatment of bacterial infections.
Structured Indications Not Available
PharmacodynamicsJosamycin is a macrolide antibiotic from Streptomyces narbonensis. The drug has antimicrobial activity against a wide spectrum of pathogens.
Mechanism of actionThe 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
50S ribosomal protein L4Proteinyes
inhibitor
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)P44345 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
PathwayCategorySMPDB ID
Josamycin Action PathwayDrug actionSMP00731
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
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
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
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
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
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
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
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 InteractionsNot 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
ATC CodesJ01FA07
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentPrematurity1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
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
SpectraNot Available
Taxonomy
DescriptionThis 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.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic oxygen compounds
Sub ClassOrganooxygen compounds
Direct ParentAminoglycosides
Alternative Parents
Substituents
  • Aminoglycoside core
  • Macrolide
  • Disaccharide
  • Glycosyl compound
  • O-glycosyl compound
  • Tricarboxylic acid or derivatives
  • Fatty acid ester
  • Fatty acyl
  • Oxane
  • Alpha-hydrogen aldehyde
  • Tertiary alcohol
  • 1,2-aminoalcohol
  • Amino acid or derivatives
  • Carboxylic acid ester
  • Lactone
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary alcohol
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Acetal
  • Oxacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organic oxide
  • Alcohol
  • Carbonyl group
  • Organopnictogen compound
  • Aldehyde
  • Organonitrogen compound
  • Organic nitrogen compound
  • Amine
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors

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 different domains of the 23S rRNA in the assembled 50S subunit and ribosome (By similarity).Protein L4 is a both a transcriptional repressor and a translational repressor protein. It regulates transcripti...
Gene Name:
rplD
Uniprot ID:
P44345
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
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 May 19, 2017 16:52