Identification
- Generic Name
- Tridolgosir
- DrugBank Accession Number
- DB02034
- Background
An indolizidine alkaloid from the plant Swainsona canescens that is a potent alpha-mannosidase inhibitor. Swainsonine also exhibits antimetastatic, antiproliferative, and immunomodulatory activity.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Tridolgosir (DB02034)
- Weight
- Average: 173.2096
Monoisotopic: 173.105193351 - Chemical Formula
- C8H15NO3
- Synonyms
- (1S,2R,8R,8AR)-octahydro-1,2,8-indolizinetriol
- Swainosine
- Tridolgosir
Pharmacology
- Indication
Not Available
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Not 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.
Target Actions Organism UAlpha-mannosidase 2 Not Available Humans - 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
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Products
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Ingredient UNII CAS InChI Key Tridolgosir hydrochloride 78KR51ES9B 214462-68-7 LIRVFCZWYJVKCV-XNJRRJNCSA-N
Categories
- Drug Categories
- Not Available
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds 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.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indolizidines
- Sub Class
- Not Available
- Direct Parent
- Indolizidines
- Alternative Parents
- Piperidines / N-alkylpyrrolidines / Trialkylamines / Secondary alcohols / 1,2-aminoalcohols / Polyols / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- 1,2-aminoalcohol / Alcohol / Aliphatic heteropolycyclic compound / Amine / Azacycle / Hydrocarbon derivative / Indolizidine / N-alkylpyrrolidine / Organic nitrogen compound / Organic oxygen compound
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- indolizidine alkaloid (CHEBI:9367) / Indolizidine alkaloids (C10173)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- RSY4RK37KQ
- CAS number
- 72741-87-8
- InChI Key
- FXUAIOOAOAVCGD-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
- [H][C@@]1(O)CN2CCC[C@@]([H])(O)[C@]2([H])[C@]1([H])O
References
- Synthesis Reference
William H. Pearson, Erik J. Hembre, "Method for preparing swainsonine." U.S. Patent US5919952, issued December, 1986.
US5919952- General References
- 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. [Article]
- External Links
- KEGG Compound
- C10173
- PubChem Compound
- 51683
- PubChem Substance
- 46506581
- ChemSpider
- 46788
- BindingDB
- 50016706
- ChEBI
- 9367
- ChEMBL
- CHEMBL371197
- ZINC
- ZINC000003875041
- PDBe Ligand
- SWA
- Wikipedia
- Swainsonine
- PDB Entries
- 1hww / 2ww0 / 2ww2 / 2wyi / 3blb
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 143-144 °C Not Available - Predicted Properties
Property Value Source Water Solubility 1320.0 mg/mL ALOGPS logP -1.5 ALOGPS logP -1.4 Chemaxon logS 0.88 ALOGPS pKa (Strongest Acidic) 13.28 Chemaxon pKa (Strongest Basic) 9.47 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 63.93 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 43.12 m3·mol-1 Chemaxon Polarizability 17.84 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9652 Blood Brain Barrier + 0.5273 Caco-2 permeable - 0.5141 P-glycoprotein substrate Substrate 0.6622 P-glycoprotein inhibitor I Non-inhibitor 0.8542 P-glycoprotein inhibitor II Non-inhibitor 0.9732 Renal organic cation transporter Non-inhibitor 0.6424 CYP450 2C9 substrate Non-substrate 0.8769 CYP450 2D6 substrate Non-substrate 0.6593 CYP450 3A4 substrate Non-substrate 0.5136 CYP450 1A2 substrate Non-inhibitor 0.7861 CYP450 2C9 inhibitor Non-inhibitor 0.9292 CYP450 2D6 inhibitor Non-inhibitor 0.9075 CYP450 2C19 inhibitor Non-inhibitor 0.9214 CYP450 3A4 inhibitor Non-inhibitor 0.9972 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9921 Ames test Non AMES toxic 0.7576 Carcinogenicity Non-carcinogens 0.9722 Biodegradation Not ready biodegradable 0.9773 Rat acute toxicity 2.3774 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.6501 hERG inhibition (predictor II) Non-inhibitor 0.8976
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 137.0190655 predictedDarkChem Lite v0.1.0 [M-H]- 136.8158655 predictedDarkChem Lite v0.1.0 [M-H]- 137.76936 predictedDeepCCS 1.0 (2019) [M+H]+ 137.5482655 predictedDarkChem Lite v0.1.0 [M+H]+ 137.2767655 predictedDarkChem Lite v0.1.0 [M+H]+ 140.30269 predictedDeepCCS 1.0 (2019) [M+Na]+ 137.0246655 predictedDarkChem Lite v0.1.0 [M+Na]+ 136.6592655 predictedDarkChem Lite v0.1.0 [M+Na]+ 148.31482 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- 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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 21, 2021 18:51