Identification
NameTridolgosir
Accession NumberDB02034  (EXPT02983, DB06425)
TypeSmall Molecule
GroupsExperimental
Description

An indolizidine alkaloid from the plant Swainsona canescens that is a potent alpha-mannosidase inhibitor. Swainsonine also exhibits antimetastatic, antiproliferative, and immunomodulatory activity.

Structure
Thumb
Synonyms
(1S,2R,8R,8AR)-octahydro-1,2,8-indolizinetriol
Swainosine
External IDs Not Available
Product Ingredients
IngredientUNIICASInChI KeyDetails
Tridolgosir hydrochloride78KR51ES9B 214462-68-7LIRVFCZWYJVKCV-XNJRRJNCSA-NDetails
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
CategoriesNot Available
UNIIRSY4RK37KQ
CAS number72741-87-8
WeightAverage: 173.2096
Monoisotopic: 173.105193351
Chemical FormulaC8H15NO3
InChI KeyFXUAIOOAOAVCGD-WCTZXXKLSA-N
InChI
InChI=1S/C8H15NO3/c10-5-2-1-3-9-4-6(11)8(12)7(5)9/h5-8,10-12H,1-4H2/t5-,6-,7-,8-/m1/s1
IUPAC Name
(1S,2R,8R,8aR)-octahydroindolizine-1,2,8-triol
SMILES
Pharmacology
IndicationNot Available
Structured Indications Not Available
PharmacodynamicsNot Available
Mechanism of action

Tridolgosir competitively inhibits the alpha manosidase II (alphaMII), which processes N linked carbohydrates of newly synthesized glycoproteins passing through the Golgi apparatus to the cell surface. Highly branched carbohydrate structures are created which bind to Lectin-phytohemagglutinin (L-PHA) and are subsequently expressed in different tumor types which results in metastatic phenotype, which is correlated with an increased aggressiveness in animals and causes other human malignancies. Inhibition of alphaMII reduces carbohydrates that bind to L-PHA, reducing aggressiveness, metastatic phenotype cells, slows tumor growth, and increases“hybrid type” carbohydrates on the cell surface. Hybrid type carbohydrates may increase cytokine activation of lymphocytes, increasing tumor susceptibility to lymphokine activated and natural killer cells.

TargetKindPharmacological actionActionsOrganismUniProt ID
Alpha-mannosidase 2ProteinunknownNot AvailableHumanQ16706 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 organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Swainsonine.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Swainsonine.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Swainsonine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Swainsonine.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Swainsonine.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Swainsonine.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Swainsonine.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Swainsonine.Approved, Investigational
OleandrinAnvirzel may decrease the cardiotoxic activities of Swainsonine.Experimental
OuabainOuabain may decrease the cardiotoxic activities of Swainsonine.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Swainsonine.Approved, Vet Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Swainsonine.Approved, Investigational
Food InteractionsNot Available
References
Synthesis Reference

William H. Pearson, Erik J. Hembre, "Method for preparing swainsonine." U.S. Patent US5919952, issued December, 1986.

US5919952
General References
  1. Shaheen PE, Stadler W, Elson P, Knox J, Winquist E, Bukowski RM: Phase II study of the efficacy and safety of oral GD0039 in patients with locally advanced or metastatic renal cell carcinoma. Invest New Drugs. 2005 Dec;23(6):577-81. [PubMed:16034517 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials Not Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)143-144 °CNot Available
Predicted Properties
PropertyValueSource
Water Solubility1320.0 mg/mLALOGPS
logP-1.5ALOGPS
logP-1.4ChemAxon
logS0.88ALOGPS
pKa (Strongest Acidic)13.28ChemAxon
pKa (Strongest Basic)9.47ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area63.93 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity43.12 m3·mol-1ChemAxon
Polarizability17.84 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9652
Blood Brain Barrier+0.5273
Caco-2 permeable-0.5141
P-glycoprotein substrateSubstrate0.6622
P-glycoprotein inhibitor INon-inhibitor0.8542
P-glycoprotein inhibitor IINon-inhibitor0.9732
Renal organic cation transporterNon-inhibitor0.6424
CYP450 2C9 substrateNon-substrate0.8769
CYP450 2D6 substrateNon-substrate0.6593
CYP450 3A4 substrateNon-substrate0.5136
CYP450 1A2 substrateNon-inhibitor0.7861
CYP450 2C9 inhibitorNon-inhibitor0.9292
CYP450 2D6 inhibitorNon-inhibitor0.9075
CYP450 2C19 inhibitorNon-inhibitor0.9214
CYP450 3A4 inhibitorNon-inhibitor0.9972
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9921
Ames testNon AMES toxic0.7576
CarcinogenicityNon-carcinogens0.9722
BiodegradationNot ready biodegradable0.9773
Rat acute toxicity2.3774 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6501
hERG inhibition (predictor II)Non-inhibitor0.8976
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-014i-2911110000-6a7c4a62604e701b490dView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as indolizidines. These are polycyclic compounds containing an indolizidine, which is a bicyclic heterocycle containing a saturated six-member ring fused to a saturated five-member ring, one of the bridging atoms being nitrogen.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassIndolizidines
Direct ParentIndolizidines
Alternative ParentsPiperidines / N-alkylpyrrolidines / Trialkylamines / Secondary alcohols / 1,2-aminoalcohols / Polyols / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
SubstituentsIndolizidine / Piperidine / N-alkylpyrrolidine / Pyrrolidine / Tertiary aliphatic amine / Tertiary amine / Secondary alcohol / 1,2-aminoalcohol / Azacycle / Polyol
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptorsindolizidine alkaloid (CHEBI:9367 ) / Indolizidine alkaloids (C10173 )

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Zinc ion binding
Specific Function:
Catalyzes the first committed step in the biosynthesis of complex N-glycans. It controls conversion of high mannose to complex N-glycans; the final hydrolytic step in the N-glycan maturation pathway.
Gene Name:
MAN2A1
Uniprot ID:
Q16706
Uniprot Name:
Alpha-mannosidase 2
Molecular Weight:
131139.485 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 ]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
Drug created on June 13, 2005 07:24 / Updated on September 01, 2017 10:47