This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Alanosine
Accession Number
DB05540
Type
Small Molecule
Groups
Investigational
Description

An amino acid analogue and antibiotic derived from the bacterium Streptomyces alanosinicus with antimetabolite and potential antineoplastic activities.

Structure
Thumb
Synonyms
  • L-Alanosine
External IDs
SDX-102
Categories
UNII
2CNI71214Y
CAS number
5854-93-3
Weight
Average: 149.1054
Monoisotopic: 149.043655727
Chemical Formula
C3H7N3O4
InChI Key
MLFKVJCWGUZWNV-REOHCLBHSA-N
InChI
InChI=1S/C3H7N3O4/c4-2(3(7)8)1-6(10)5-9/h2,10H,1,4H2,(H,7,8)/t2-/m0/s1
IUPAC Name
(2S)-2-amino-3-[hydroxy(nitroso)amino]propanoic acid
SMILES
N[[email protected]@H](CN(O)N=O)C(O)=O

Pharmacology

Indication

Investigated for use/treatment in brain cancer and cancer/tumors (unspecified).

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

L-alanosine inhibits adenylosuccinate synthetase, which converts inosine monophospate (IMP) into adenylosuccinate, an intermediate in purine metabolism. L-alanosine-induced disruption of de novo purine biosynthesis is potentiated by methylthioadenosine phosphorylase (MTAP) deficiency.

TargetActionsOrganism
UAspartate carbamoyltransferase catalytic chainNot AvailableEscherichia coli (strain K12)
UAdenylosuccinate synthetase isozyme 2Not AvailableHuman
UAdenylosuccinate synthetase isozyme 1Not AvailableHuman
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
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Alanosine.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Alanosine.Experimental
AncestimThe risk or severity of cytotoxicity can be increased when Ancestim is combined with Alanosine.Approved, Investigational, Withdrawn
BevacizumabBevacizumab may increase the cardiotoxic activities of Alanosine.Approved, Investigational
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Alanosine.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Alanosine.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Alanosine.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Alanosine.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Alanosine.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Alanosine.Approved
GitoformateGitoformate may decrease the cardiotoxic activities of Alanosine.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Alanosine.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Alanosine.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Alanosine.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Alanosine.Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Alanosine.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Alanosine.Experimental
Technetium Tc-99m oxidronateAlanosine can cause a decrease in the absorption of Technetium Tc-99m oxidronate resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Alanosine.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Kindler HL, Burris HA 3rd, Sandler AB, Oliff IA: A phase II multicenter study of L-alanosine, a potent inhibitor of adenine biosynthesis, in patients with MTAP-deficient cancer. Invest New Drugs. 2009 Feb;27(1):75-81. doi: 10.1007/s10637-008-9160-1. Epub 2008 Jul 11. [PubMed:18618081]
  2. Huang Y, Dai Z, Barbacioru C, Sadee W: Cystine-glutamate transporter SLC7A11 in cancer chemosensitivity and chemoresistance. Cancer Res. 2005 Aug 15;65(16):7446-54. [PubMed:16103098]
External Links
PubChem Compound
22128
PubChem Substance
8166290
ChemSpider
20787
ChEMBL
CHEMBL452715
HET
AL0
Wikipedia
Alanosine
PDB Entries
2air

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentBrain and Central Nervous System Tumors1
2CompletedTreatmentLung Cancers / Malignant Neoplasm of Pancreas / Mesothelioma, Malignant / Sarcomas1

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 Solubility20.7 mg/mLALOGPS
logP-2.8ALOGPS
logP-3.6ChemAxon
logS-0.86ALOGPS
pKa (Strongest Acidic)1.5ChemAxon
pKa (Strongest Basic)8.67ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area116.22 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity30.7 m3·mol-1ChemAxon
Polarizability11.94 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6523
Blood Brain Barrier-0.6928
Caco-2 permeable-0.6474
P-glycoprotein substrateNon-substrate0.6806
P-glycoprotein inhibitor INon-inhibitor0.9116
P-glycoprotein inhibitor IINon-inhibitor0.9908
Renal organic cation transporterNon-inhibitor0.9589
CYP450 2C9 substrateNon-substrate0.907
CYP450 2D6 substrateNon-substrate0.8242
CYP450 3A4 substrateNon-substrate0.6489
CYP450 1A2 substrateNon-inhibitor0.8735
CYP450 2C9 inhibitorNon-inhibitor0.8825
CYP450 2D6 inhibitorNon-inhibitor0.937
CYP450 2C19 inhibitorNon-inhibitor0.854
CYP450 3A4 inhibitorNon-inhibitor0.9525
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9913
Ames testAMES toxic0.804
CarcinogenicityNon-carcinogens0.607
BiodegradationNot ready biodegradable0.7679
Rat acute toxicity2.1600 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9844
hERG inhibition (predictor II)Non-inhibitor0.9319
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 l-alpha-amino acids. These are alpha amino acids which have the L-configuration of the alpha-carbon atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
L-alpha-amino acids
Alternative Parents
Organic N-nitroso compounds / Amino acids / N-organohydroxylamines / Monocarboxylic acids and derivatives / Carboxylic acids / Organopnictogen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives / Carbonyl compounds
Substituents
L-alpha-amino acid / Organic n-nitroso compound / Amino acid / Organic nitroso compound / Carboxylic acid / Monocarboxylic acid or derivatives / N-organohydroxylamine / Amine / Hydrocarbon derivative / Organic oxide
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Amino acid binding
Gene Name
pyrB
Uniprot ID
P0A786
Uniprot Name
Aspartate carbamoyltransferase catalytic subunit
Molecular Weight
34427.02 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Phosphate ion binding
Specific Function
Plays an important role in the de novo pathway and in the salvage pathway of purine nucleotide biosynthesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP.
Gene Name
ADSS
Uniprot ID
P30520
Uniprot Name
Adenylosuccinate synthetase isozyme 2
Molecular Weight
50097.075 Da
References
  1. Datta SK, Guicherit OM, Kellems RE: Adenylosuccinate synthetase: a dominant amplifiable genetic marker in mammalian cells. Somat Cell Mol Genet. 1994 Sep;20(5):381-9. [PubMed:7825060]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Phosphate ion binding
Specific Function
Component of the purine nucleotide cycle (PNC), which interconverts IMP and AMP to regulate the nucleotide levels in various tissues, and which contributes to glycolysis and ammoniagenesis. Catalyz...
Gene Name
ADSSL1
Uniprot ID
Q8N142
Uniprot Name
Adenylosuccinate synthetase isozyme 1
Molecular Weight
50208.16 Da
References
  1. Datta SK, Guicherit OM, Kellems RE: Adenylosuccinate synthetase: a dominant amplifiable genetic marker in mammalian cells. Somat Cell Mol Genet. 1994 Sep;20(5):381-9. [PubMed:7825060]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Cystine:glutamate antiporter activity
Specific Function
Sodium-independent, high-affinity exchange of anionic amino acids with high specificity for anionic form of cystine and glutamate.
Gene Name
SLC7A11
Uniprot ID
Q9UPY5
Uniprot Name
Cystine/glutamate transporter
Molecular Weight
55422.44 Da
References
  1. Huang Y, Dai Z, Barbacioru C, Sadee W: Cystine-glutamate transporter SLC7A11 in cancer chemosensitivity and chemoresistance. Cancer Res. 2005 Aug 15;65(16):7446-54. [PubMed:16103098]

Drug created on November 18, 2007 11:25 / Updated on December 01, 2017 15:36