Sinefungin

Identification

Name
Sinefungin
Accession Number
DB01910  (EXPT02890)
Type
Small Molecule
Groups
Experimental
Description

Sinefungin is a solid. This compound belongs to the purine nucleosides and analogues. These are compounds comprising a purine base attached to a sugar. The proteins that adenosyl-ornithine target include RdmB, modification methylase TaqI, rRNA (adenine-N6-)-methyltransferase, and modification methylase RsrI.

Structure
Thumb
Synonyms
  • (2S,5S)-2,5-diamino-6-[(2R,3S,R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]hexanoic acid
  • 6,9-Diamino-1-(6-amino-9H-purin-9-yl)-1,5,6,7,8,9-hexadeoxy-beta-D-ribo-decofuranuronic acid
  • 6,9-Diamino-1-(6-amino-9H-purin-9-yl)-1,5,6,7,8,9-hexadeoxydecofuranuronic acid
  • Adenosyl-ornithine
  • sinefungina
  • sinefungine
  • sinefunginum
External IDs
A 9145 / Antibiotic A 9145 / LILLY 57926 / LY-57926
Categories
UNII
W2U467CIIL
CAS number
58944-73-3
Weight
Average: 381.387
Monoisotopic: 381.176066881
Chemical Formula
C15H23N7O5
InChI Key
LMXOHSDXUQEUSF-YECHIGJVSA-N
InChI
InChI=1S/C15H23N7O5/c16-6(1-2-7(17)15(25)26)3-8-10(23)11(24)14(27-8)22-5-21-9-12(18)19-4-20-13(9)22/h4-8,10-11,14,23-24H,1-3,16-17H2,(H,25,26)(H2,18,19,20)/t6-,7-,8+,10+,11+,14+/m0/s1
IUPAC Name
(2S,5S)-2,5-diamino-6-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]hexanoic acid
SMILES
[H][[email protected]](N)(CC[[email protected]]([H])(N)C(O)=O)C[[email protected]@]1([H])O[[email protected]@]([H])(N2C=NC3=C(N)N=CN=C23)[[email protected]]([H])(O)[[email protected]]1([H])O

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UModification methylase RsrINot AvailableRhodobacter sphaeroides
URdmBNot AvailableStreptomyces purpurascens
UrRNA adenine N-6-methyltransferaseNot AvailableBacillus subtilis
UModification methylase TaqINot AvailableThermus aquaticus
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
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcepromazineThe serum concentration of Acepromazine can be increased when it is combined with Sinefungin.Approved, Vet Approved
AceprometazineThe serum concentration of Aceprometazine can be increased when it is combined with Sinefungin.Approved
AlimemazineThe serum concentration of Alimemazine can be increased when it is combined with Sinefungin.Approved, Vet Approved
AmlodipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Amlodipine.Approved
Amphotericin BThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Sinefungin.Approved, Investigational
AmrinoneThe risk or severity of adverse effects can be increased when Sinefungin is combined with Amrinone.Approved
ArtemetherThe risk or severity of adverse effects can be increased when Artemether is combined with Sinefungin.Approved
AzelnidipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Azelnidipine.Approved, Investigational
AzimilideThe risk or severity of adverse effects can be increased when Sinefungin is combined with Azimilide.Investigational
BarnidipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Barnidipine.Approved
BencyclaneThe risk or severity of adverse effects can be increased when Sinefungin is combined with Bencyclane.Experimental
BenidipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Benidipine.Approved, Investigational
BepridilThe risk or severity of adverse effects can be increased when Sinefungin is combined with Bepridil.Approved, Withdrawn
BL-1020The serum concentration of BL-1020 can be increased when it is combined with Sinefungin.Investigational
BuspironeThe metabolism of Buspirone can be decreased when combined with Sinefungin.Approved, Investigational
BusulfanThe serum concentration of Busulfan can be increased when it is combined with Sinefungin.Approved, Investigational
CarboxyamidotriazoleThe risk or severity of adverse effects can be increased when Sinefungin is combined with Carboxyamidotriazole.Investigational
CaroverineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Caroverine.Experimental
ChlorproethazineThe serum concentration of Chlorproethazine can be increased when it is combined with Sinefungin.Experimental
ChlorpromazineThe serum concentration of Chlorpromazine can be increased when it is combined with Sinefungin.Approved, Vet Approved
CilnidipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Cilnidipine.Approved, Investigational
CinnarizineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Cinnarizine.Approved, Investigational
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Sinefungin.Approved, Investigational, Withdrawn
ClevidipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Clevidipine.Approved
ConivaptanThe metabolism of Conivaptan can be decreased when combined with Sinefungin.Approved, Investigational
CyclosporineThe metabolism of Cyclosporine can be decreased when combined with Sinefungin.Approved, Investigational, Vet Approved
DapsoneThe risk or severity of adverse effects can be increased when Sinefungin is combined with Dapsone.Approved, Investigational
DarodipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Darodipine.Experimental
DidanosineDidanosine can cause a decrease in the absorption of Sinefungin resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
DiltiazemThe risk or severity of adverse effects can be increased when Sinefungin is combined with Diltiazem.Approved
DocetaxelThe metabolism of Docetaxel can be decreased when combined with Sinefungin.Approved, Investigational
DofetilideThe metabolism of Dofetilide can be decreased when combined with Sinefungin.Approved
DotarizineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Dotarizine.Investigational
EfonidipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Efonidipine.Approved, Investigational
EperisoneThe risk or severity of adverse effects can be increased when Sinefungin is combined with Eperisone.Approved, Investigational
EtravirineThe serum concentration of Etravirine can be increased when it is combined with Sinefungin.Approved
FelodipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Felodipine.Approved, Investigational
FendilineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Fendiline.Withdrawn
FlunarizineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Flunarizine.Approved
FluphenazineThe serum concentration of Fluphenazine can be increased when it is combined with Sinefungin.Approved
FosphenytoinThe serum concentration of Sinefungin can be decreased when it is combined with Fosphenytoin.Approved
GabapentinThe risk or severity of adverse effects can be increased when Sinefungin is combined with Gabapentin.Approved, Investigational
GallopamilThe risk or severity of adverse effects can be increased when Sinefungin is combined with Gallopamil.Investigational
IsradipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Isradipine.Approved
LacidipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Lacidipine.Approved, Investigational
LamotrigineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Lamotrigine.Approved, Investigational
LercanidipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Lercanidipine.Approved, Investigational
LidoflazineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Lidoflazine.Experimental
LosartanThe metabolism of Losartan can be decreased when combined with Sinefungin.Approved
LumefantrineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Lumefantrine.Approved
Magnesium SulfateThe risk or severity of adverse effects can be increased when Sinefungin is combined with Magnesium Sulfate.Approved, Vet Approved
ManidipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Manidipine.Approved, Investigational
MesoridazineThe serum concentration of Mesoridazine can be increased when it is combined with Sinefungin.Approved, Investigational
MethotrimeprazineThe serum concentration of Methotrimeprazine can be increased when it is combined with Sinefungin.Approved
Methylene blueThe serum concentration of Methylene blue can be increased when it is combined with Sinefungin.Approved, Investigational
MibefradilThe risk or severity of adverse effects can be increased when Sinefungin is combined with Mibefradil.Investigational, Withdrawn
MoricizineThe serum concentration of Moricizine can be increased when it is combined with Sinefungin.Approved, Investigational, Withdrawn
NaftopidilThe risk or severity of adverse effects can be increased when Sinefungin is combined with Naftopidil.Investigational
NicardipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Nicardipine.Approved
NifedipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Nifedipine.Approved
NiguldipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Niguldipine.Experimental
NiludipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Niludipine.Experimental
NilvadipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Nilvadipine.Approved, Investigational
NimesulideThe risk or severity of adverse effects can be increased when Sinefungin is combined with Nimesulide.Approved, Investigational, Withdrawn
NimodipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Nimodipine.Approved
NisoldipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Nisoldipine.Approved
NitrendipineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Nitrendipine.Approved, Investigational
OtiloniumThe risk or severity of adverse effects can be increased when Sinefungin is combined with Otilonium.Experimental, Investigational
PerazineThe serum concentration of Perazine can be increased when it is combined with Sinefungin.Investigational
PerhexilineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Perhexiline.Approved, Investigational
PerphenazineThe serum concentration of Perphenazine can be increased when it is combined with Sinefungin.Approved
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Sinefungin.Approved, Vet Approved
PimozideSinefungin may increase the arrhythmogenic activities of Pimozide.Approved
PinaveriumThe risk or severity of adverse effects can be increased when Sinefungin is combined with Pinaverium.Approved
PregabalinThe risk or severity of adverse effects can be increased when Sinefungin is combined with Pregabalin.Approved, Illicit, Investigational
PrenylamineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Prenylamine.Withdrawn
ProchlorperazineThe serum concentration of Prochlorperazine can be increased when it is combined with Sinefungin.Approved, Vet Approved
ProgesteroneThe therapeutic efficacy of Progesterone can be decreased when used in combination with Sinefungin.Approved, Vet Approved
PromazineThe serum concentration of Promazine can be increased when it is combined with Sinefungin.Approved, Vet Approved
PromethazineThe serum concentration of Promethazine can be increased when it is combined with Sinefungin.Approved
PropericiazineThe serum concentration of Propericiazine can be increased when it is combined with Sinefungin.Approved
PropiopromazineThe serum concentration of Propiopromazine can be increased when it is combined with Sinefungin.Vet Approved
QuinidineThe metabolism of Quinidine can be decreased when combined with Sinefungin.Approved
RanolazineThe metabolism of Ranolazine can be decreased when combined with Sinefungin.Approved, Investigational
RifabutinThe serum concentration of Rifabutin can be increased when it is combined with Sinefungin.Approved
RifampicinThe serum concentration of Rifampicin can be increased when it is combined with Sinefungin.Approved
RifapentineThe serum concentration of Rifapentine can be increased when it is combined with Sinefungin.Approved
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Sinefungin.Approved, Investigational
RisedronateThe risk or severity of adverse effects can be increased when Sinefungin is combined with Risedronate.Approved, Investigational
SolifenacinThe metabolism of Solifenacin can be decreased when combined with Sinefungin.Approved
SucralfateSucralfate can cause a decrease in the absorption of Sinefungin resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
SunitinibThe metabolism of Sunitinib can be decreased when combined with Sinefungin.Approved, Investigational
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Sinefungin.Approved, Investigational
TerodilineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Terodiline.Experimental
TetrahydropalmatineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Tetrahydropalmatine.Investigational
ThiazinamThe serum concentration of Thiazinam can be increased when it is combined with Sinefungin.Experimental
ThiethylperazineThe serum concentration of Thiethylperazine can be increased when it is combined with Sinefungin.Withdrawn
ThioproperazineThe serum concentration of Thioproperazine can be increased when it is combined with Sinefungin.Approved
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Sinefungin.Approved, Withdrawn
Tolfenamic AcidThe risk or severity of adverse effects can be increased when Sinefungin is combined with Tolfenamic Acid.Approved
TranilastThe risk or severity of adverse effects can be increased when Sinefungin is combined with Tranilast.Approved, Investigational
TrifluoperazineThe serum concentration of Trifluoperazine can be increased when it is combined with Sinefungin.Approved
TriflupromazineThe serum concentration of Triflupromazine can be increased when it is combined with Sinefungin.Approved, Vet Approved
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Sinefungin.Approved
VerapamilThe risk or severity of adverse effects can be increased when Sinefungin is combined with Verapamil.Approved
VinpocetineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Vinpocetine.Investigational
XylometazolineThe risk or severity of adverse effects can be increased when Sinefungin is combined with Xylometazoline.Approved
ZiconotideThe risk or severity of adverse effects can be increased when Sinefungin is combined with Ziconotide.Approved
ZolpidemThe serum concentration of Zolpidem can be increased when it is combined with Sinefungin.Approved
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D05846
PubChem Compound
65482
PubChem Substance
46508037
ChemSpider
58931
BindingDB
50378739
ChEBI
45453
ChEMBL
CHEMBL1214186
HET
SFG
PDB Entries
1aqj / 1nw6 / 1qaq / 1xdu / 1yfl / 2h2j / 2hv9 / 2xva / 2xyr / 2y1w
show 60 more

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility4.63 mg/mLALOGPS
logP-3ALOGPS
logP-5.1ChemAxon
logS-1.9ALOGPS
pKa (Strongest Acidic)1.95ChemAxon
pKa (Strongest Basic)10.18ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area208.65 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity92.68 m3·mol-1ChemAxon
Polarizability37.69 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8761
Blood Brain Barrier+0.5494
Caco-2 permeable-0.8305
P-glycoprotein substrateSubstrate0.5
P-glycoprotein inhibitor INon-inhibitor0.9415
P-glycoprotein inhibitor IINon-inhibitor0.9378
Renal organic cation transporterNon-inhibitor0.9402
CYP450 2C9 substrateNon-substrate0.866
CYP450 2D6 substrateNon-substrate0.8329
CYP450 3A4 substrateNon-substrate0.5259
CYP450 1A2 substrateNon-inhibitor0.8975
CYP450 2C9 inhibitorNon-inhibitor0.93
CYP450 2D6 inhibitorNon-inhibitor0.9419
CYP450 2C19 inhibitorNon-inhibitor0.9085
CYP450 3A4 inhibitorNon-inhibitor0.8717
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9296
Ames testNon AMES toxic0.7312
CarcinogenicityNon-carcinogens0.9336
BiodegradationNot ready biodegradable0.9707
Rat acute toxicity2.3802 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9855
hERG inhibition (predictor II)Non-inhibitor0.9144
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 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 5'-deoxyribonucleosides. These are nucleosides in which the oxygen atom at the 5'position of the ribose moiety has been replaced by another atom. The nucleobases here are limited to purine, pyrimidine, and pyridine derivatives.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
5'-deoxyribonucleosides
Sub Class
Not Available
Direct Parent
5'-deoxyribonucleosides
Alternative Parents
Glycosylamines / 6-aminopurines / Pentoses / L-alpha-amino acids / Medium-chain fatty acids / Amino fatty acids / Aminopyrimidines and derivatives / Heterocyclic fatty acids / Hydroxy fatty acids / N-substituted imidazoles
show 15 more
Substituents
5'-deoxyribonucleoside / N-glycosyl compound / Glycosyl compound / Pentose monosaccharide / 6-aminopurine / L-alpha-amino acid / Alpha-amino acid or derivatives / Alpha-amino acid / Imidazopyrimidine / Purine
show 38 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
adenosines, non-proteinogenic alpha-amino acid (CHEBI:45453)

Targets

Kind
Protein
Organism
Rhodobacter sphaeroides
Pharmacological action
Unknown
General Function
Site-specific dna-methyltransferase (adenine-specific) activity
Specific Function
This methylase recognizes the double-stranded sequence GAATTC, causes specific methylation on A-? on both strands, and protects the DNA from cleavage by the RsrI endonuclease.
Gene Name
rsrIM
Uniprot ID
P14751
Uniprot Name
Modification methylase RsrI
Molecular Weight
35654.88 Da
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]
Kind
Protein
Organism
Streptomyces purpurascens
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Not Available
Gene Name
rdmB
Uniprot ID
Q54527
Uniprot Name
Aclacinomycin 10-hydroxylase RdmB
Molecular Weight
39796.525 Da
Kind
Protein
Organism
Bacillus subtilis
Pharmacological action
Unknown
General Function
Rrna (adenine-n6,n6-)-dimethyltransferase activity
Specific Function
This protein produces a dimethylation of the adenine residue at position 2085 in 23S rRNA, resulting in reduced affinity between ribosomes and macrolide-lincosamide-streptogramin B antibiotics.
Gene Name
ermC'
Uniprot ID
P13956
Uniprot Name
rRNA adenine N-6-methyltransferase
Molecular Weight
28907.235 Da
Kind
Protein
Organism
Thermus aquaticus
Pharmacological action
Unknown
General Function
Site-specific dna-methyltransferase (adenine-specific) activity
Specific Function
This methylase recognizes the double-stranded sequence TCGA, causes specific methylation on A-4 on both strands and protects the DNA from cleavage by the TaqI endonuclease.
Gene Name
taqIM
Uniprot ID
P14385
Uniprot Name
Modification methylase TaqI
Molecular Weight
47861.91 Da

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 14:50