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][C@](N)(CC[C@]([H])(N)C(O)=O)C[C@@]1([H])O[C@@]([H])(N2C=NC3=C(N)N=CN=C23)[C@]([H])(O)[C@]1([H])O

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
URdmBNot AvailableStreptomyces purpurascens
UrRNA adenine N-6-methyltransferaseNot AvailableBacillus subtilis
UModification methylase TaqINot AvailableThermus aquaticus
UModification methylase RsrINot AvailableRhodobacter sphaeroides
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
AgmatineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Agmatine.Experimental, Investigational
AlimemazineThe serum concentration of Alimemazine can be increased when it is combined with Sinefungin.Approved, Vet Approved
AmiodaroneThe therapeutic efficacy of Sinefungin can be increased when used in combination with Amiodarone.Approved, Investigational
Amphotericin BThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Sinefungin.Approved, Investigational
AmrinoneThe therapeutic efficacy of Sinefungin can be increased when used in combination with Amrinone.Approved
AranidipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Aranidipine.Approved, Investigational
ArtemetherThe risk or severity of QTc prolongation can be increased when Sinefungin is combined with Artemether.Approved
AzelnidipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Azelnidipine.Approved, Investigational
AzimilideThe therapeutic efficacy of Sinefungin can be increased when used in combination with Azimilide.Investigational
BarnidipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Barnidipine.Approved
BencyclaneThe therapeutic efficacy of Sinefungin can be increased when used in combination with Bencyclane.Experimental
BenidipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Benidipine.Approved, Investigational
BepridilThe therapeutic efficacy of Sinefungin can be increased when used in combination with Bepridil.Approved, Withdrawn
BioallethrinThe therapeutic efficacy of Sinefungin can be increased when used in combination with Bioallethrin.Approved, Experimental
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 therapeutic efficacy of Sinefungin can be increased when used in combination with Carboxyamidotriazole.Investigational
CaroverineThe therapeutic efficacy of Sinefungin can be increased when used in combination 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, Investigational, Vet Approved
CilnidipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Cilnidipine.Approved, Investigational
CinnarizineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Cinnarizine.Approved, Investigational
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Sinefungin.Approved, Investigational, Withdrawn
ClevidipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Clevidipine.Approved, Investigational
CyclandelateThe therapeutic efficacy of Sinefungin can be increased when used in combination with Cyclandelate.Approved
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 therapeutic efficacy of Sinefungin can be increased when used in combination 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 therapeutic efficacy of Sinefungin can be increased when used in combination with Diltiazem.Approved, Investigational
DocetaxelThe metabolism of Docetaxel can be decreased when combined with Sinefungin.Approved, Investigational
DofetilideThe serum concentration of Dofetilide can be increased when it is combined with Sinefungin.Approved, Investigational
DotarizineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Dotarizine.Investigational
EfonidipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Efonidipine.Approved, Investigational
EperisoneThe therapeutic efficacy of Sinefungin can be increased when used in combination with Eperisone.Approved, Investigational
EthosuximideThe therapeutic efficacy of Sinefungin can be increased when used in combination with Ethosuximide.Approved
EtravirineThe serum concentration of Etravirine can be increased when it is combined with Sinefungin.Approved
FelodipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Felodipine.Approved, Investigational
FendilineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Fendiline.Withdrawn
Fish oilThe therapeutic efficacy of Sinefungin can be increased when used in combination with Fish oil.Approved, Nutraceutical
FlunarizineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Flunarizine.Approved
FluphenazineThe serum concentration of Fluphenazine can be increased when it is combined with Sinefungin.Approved
FluspirileneThe therapeutic efficacy of Sinefungin can be increased when used in combination with Fluspirilene.Approved, Investigational
FosphenytoinThe serum concentration of Sinefungin can be decreased when it is combined with Fosphenytoin.Approved, Investigational
GabapentinThe therapeutic efficacy of Sinefungin can be increased when used in combination with Gabapentin.Approved, Investigational
GallopamilThe therapeutic efficacy of Sinefungin can be increased when used in combination with Gallopamil.Investigational
IsradipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Isradipine.Approved, Investigational
LacidipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Lacidipine.Approved, Investigational
LamotrigineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Lamotrigine.Approved, Investigational
LercanidipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Lercanidipine.Approved, Investigational
LevetiracetamThe therapeutic efficacy of Sinefungin can be increased when used in combination with Levetiracetam.Approved, Investigational
LidoflazineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Lidoflazine.Experimental
LoperamideThe therapeutic efficacy of Sinefungin can be increased when used in combination with Loperamide.Approved
LosartanThe metabolism of Losartan can be decreased when combined with Sinefungin.Approved
LumefantrineThe risk or severity of QTc prolongation can be increased when Sinefungin is combined with Lumefantrine.Approved
Magnesium sulfateThe therapeutic efficacy of Sinefungin can be increased when used in combination with Magnesium sulfate.Approved, Investigational, Vet Approved
ManidipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Manidipine.Approved, Investigational
MentholThe therapeutic efficacy of Sinefungin can be increased when used in combination with Menthol.Approved
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, Investigational
MethsuximideThe therapeutic efficacy of Sinefungin can be increased when used in combination with Methsuximide.Approved
Methylene blueThe serum concentration of Methylene blue can be increased when it is combined with Sinefungin.Approved, Investigational
MibefradilThe therapeutic efficacy of Sinefungin can be increased when used in combination with Mibefradil.Investigational, Withdrawn
MoricizineThe serum concentration of Moricizine can be increased when it is combined with Sinefungin.Approved, Investigational, Withdrawn
NaftopidilThe therapeutic efficacy of Sinefungin can be increased when used in combination with Naftopidil.Investigational
NicardipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Nicardipine.Approved, Investigational
NifedipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Nifedipine.Approved
NiguldipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Niguldipine.Experimental
NiludipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Niludipine.Experimental
NilvadipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Nilvadipine.Approved, Investigational
NimesulideThe therapeutic efficacy of Sinefungin can be increased when used in combination with Nimesulide.Approved, Investigational, Withdrawn
NimodipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Nimodipine.Approved, Investigational
NisoldipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Nisoldipine.Approved
NitrendipineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Nitrendipine.Approved, Investigational
NylidrinThe therapeutic efficacy of Sinefungin can be increased when used in combination with Nylidrin.Approved
OtiloniumThe therapeutic efficacy of Sinefungin can be increased when used in combination with Otilonium.Experimental, Investigational
PerazineThe serum concentration of Perazine can be increased when it is combined with Sinefungin.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
PinaveriumThe therapeutic efficacy of Sinefungin can be increased when used in combination with Pinaverium.Approved
PrenylamineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Prenylamine.Withdrawn
ProchlorperazineThe serum concentration of Prochlorperazine can be increased when it is combined with Sinefungin.Approved, Vet Approved
ProgesteroneThe absorption of Progesterone can be decreased when combined 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, Investigational
PropericiazineThe serum concentration of Propericiazine can be increased when it is combined with Sinefungin.Approved, Investigational
PropiopromazineThe serum concentration of Propiopromazine can be increased when it is combined with Sinefungin.Vet Approved
QuinidineThe serum concentration of Quinidine can be increased when it is combined with Sinefungin.Approved, Investigational
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Sinefungin.Approved, Investigational
RifabutinThe serum concentration of Rifabutin can be increased when it is combined with Sinefungin.Approved, Investigational
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, Investigational
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Sinefungin.Approved, Investigational
SeletracetamThe therapeutic efficacy of Sinefungin can be increased when used in combination with Seletracetam.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 therapeutic efficacy of Sinefungin can be increased when used in combination with Terodiline.Experimental
TetrahydropalmatineThe therapeutic efficacy of Sinefungin can be increased when used in combination 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 therapeutic efficacy of Sinefungin can be increased when used in combination with Tolfenamic Acid.Approved, Investigational
TranilastThe therapeutic efficacy of Sinefungin can be increased when used in combination with Tranilast.Approved, Investigational
TrifluoperazineThe serum concentration of Trifluoperazine can be increased when it is combined with Sinefungin.Approved, Investigational
TriflupromazineThe serum concentration of Triflupromazine can be increased when it is combined with Sinefungin.Approved, Vet Approved
TrimebutineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Trimebutine.Approved
TrimethadioneThe therapeutic efficacy of Sinefungin can be increased when used in combination with Trimethadione.Approved
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Sinefungin.Approved
VerapamilThe therapeutic efficacy of Sinefungin can be increased when used in combination with Verapamil.Approved
VinpocetineThe therapeutic efficacy of Sinefungin can be increased when used in combination with Vinpocetine.Investigational
WIN 55212-2The therapeutic efficacy of Sinefungin can be increased when used in combination with WIN 55212-2.Experimental
ZiconotideThe therapeutic efficacy of Sinefungin can be increased when used in combination with Ziconotide.Approved
ZolpidemThe serum concentration of Zolpidem can be increased when it is combined with Sinefungin.Approved
ZonisamideThe therapeutic efficacy of Sinefungin can be increased when used in combination with Zonisamide.Approved, Investigational
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 65 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
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
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]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 04:43