Tagetitoxin
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Identification
- Generic Name
- Tagetitoxin
- DrugBank Accession Number
- DB04788
- Background
Tagetitoxin is a bacterial phytotoxin. It preferentially inhibits eukaryotic RNA polymerase.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
- Weight
- Average: 416.298
Monoisotopic: 416.029066598 - Chemical Formula
- C11H17N2O11PS
- Synonyms
- (1R,4R,5R,6R,7S,8R)-6-Acetoxy-7-amino-4-carbamoyl-4-hydroxy-8-(phosphonooxy)-9-oxa-3-thiabicyclo[3.3.1]nonane-1-carboxylic acid
Pharmacology
- Indication
Not Available
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- Pharmacodynamics
Not Available
- Mechanism of action
Tagetitoxin inhibits all RNAP catalytic reactions. Tagetitoxin binding is mediated exclusively through polar interactions with the beta and beta' residues whose substitutions confer resistance to tagetitoxin in vitro.
Target Actions Organism UDNA-directed RNA polymerase subunit beta Not Available Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579) UDNA-directed RNA polymerase subunit beta' Not Available Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579) - 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
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as delta amino acids and derivatives. These are compounds containing a carboxylic acid group and an amino group at the C5 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
- Delta amino acids and derivatives
- Alternative Parents
- Gamma amino acids and derivatives / Monoalkyl phosphates / Pyrans / Oxathianes / Oxanes / Dicarboxylic acids and derivatives / Monosaccharides / Primary carboxylic acid amides / Amino acids / Carboxylic acid esters show 8 more
- Substituents
- 1,4-oxathiane / Aliphatic heteropolycyclic compound / Alkyl phosphate / Amine / Amino acid / Carbonyl group / Carboxamide group / Carboxylic acid / Carboxylic acid ester / Delta amino acid or derivatives show 22 more
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- Not Available
- CAS number
- 87913-21-1
- InChI Key
- UVAAUIDYGIWLMB-HGNFPZBQSA-N
- InChI
- InChI=1S/C11H17N2O11PS/c1-3(14)22-5-4(12)6(24-25(19,20)21)10(9(16)17)2-26-11(18,8(13)15)7(5)23-10/h4-7,18H,2,12H2,1H3,(H2,13,15)(H,16,17)(H2,19,20,21)/t4-,5+,6+,7+,10+,11+/m0/s1
- IUPAC Name
- (1R,4R,5R,6R,7S,8R)-6-(acetyloxy)-7-amino-4-carbamoyl-4-hydroxy-8-(phosphonooxy)-9-oxa-3-thiabicyclo[3.3.1]nonane-1-carboxylic acid
- SMILES
- [H]N([H])[C@H]1[C@@H](OC(C)=O)[C@@]2([H])O[C@](CS[C@@]2(O)C(=O)N([H])[H])([C@@H]1OP(O)(O)=O)C(O)=O
References
- General References
- Plet JR, Porter MJ: Synthesis of the bicyclic core of tagetitoxin. Chem Commun (Camb). 2006 Mar 21;(11):1197-9. Epub 2006 Feb 14. [Article]
- Vassylyev DG, Svetlov V, Vassylyeva MN, Perederina A, Igarashi N, Matsugaki N, Wakatsuki S, Artsimovitch I: Structural basis for transcription inhibition by tagetitoxin. Nat Struct Mol Biol. 2005 Dec;12(12):1086-93. Epub 2005 Nov 6. [Article]
- Mathews DE, Durbin RD: Mechanistic aspects of tagetitoxin inhibition of RNA polymerase from Escherichia coli. Biochemistry. 1994 Oct 4;33(39):11987-92. [Article]
- Steinberg TH, Mathews DE, Durbin RD, Burgess RR: Tagetitoxin: a new inhibitor of eukaryotic transcription by RNA polymerase III. J Biol Chem. 1990 Jan 5;265(1):499-505. [Article]
- External Links
- PubChem Compound
- 5327077
- PubChem Substance
- 46506068
- ChemSpider
- 4484333
- ZINC
- ZINC000012504512
- PDBe Ligand
- TGT
- Wikipedia
- Tagetitoxin
- PDB Entries
- 2be5
Clinical Trials
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
Property Value Source Water Solubility 37.5 mg/mL ALOGPS logP -1.5 ALOGPS logP -3.8 Chemaxon logS -1 ALOGPS pKa (Strongest Acidic) 0.85 Chemaxon pKa (Strongest Basic) 8.72 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 10 Chemaxon Hydrogen Donor Count 6 Chemaxon Polar Surface Area 228.93 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 80.58 m3·mol-1 Chemaxon Polarizability 34.21 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.9526 Blood Brain Barrier - 0.8728 Caco-2 permeable - 0.678 P-glycoprotein substrate Non-substrate 0.5244 P-glycoprotein inhibitor I Non-inhibitor 0.755 P-glycoprotein inhibitor II Non-inhibitor 1.0 Renal organic cation transporter Non-inhibitor 0.9637 CYP450 2C9 substrate Non-substrate 0.6653 CYP450 2D6 substrate Non-substrate 0.8187 CYP450 3A4 substrate Non-substrate 0.5 CYP450 1A2 substrate Non-inhibitor 0.7787 CYP450 2C9 inhibitor Non-inhibitor 0.8173 CYP450 2D6 inhibitor Non-inhibitor 0.9095 CYP450 2C19 inhibitor Non-inhibitor 0.793 CYP450 3A4 inhibitor Non-inhibitor 0.892 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9468 Ames test Non AMES toxic 0.5863 Carcinogenicity Non-carcinogens 0.9072 Biodegradation Not ready biodegradable 0.9783 Rat acute toxicity 2.5607 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9967 hERG inhibition (predictor II) Non-inhibitor 0.8383
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0005-9302000000-a6f854df9ca6b9d05d7f Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-0001900000-a882debbf55a3e8e98a8 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-3001900000-315a9c68a5a0c7207e85 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0uy0-0209300000-7fc101c6d6e66cbbcb3c Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0fb9-3009000000-e0140bbf5306e6bf0ccb Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0l2o-0495000000-8b587a8c5736341dd983 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-9000100000-3a0eaf62c3ae11090404 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 163.1676 predictedDeepCCS 1.0 (2019) [M+H]+ 165.56317 predictedDeepCCS 1.0 (2019) [M+Na]+ 171.55873 predictedDeepCCS 1.0 (2019)
Targets
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1. DetailsDNA-directed RNA polymerase subunit beta
- Kind
- Protein
- Organism
- Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
- Pharmacological action
- Unknown
- General Function
- Ribonucleoside binding
- Specific Function
- DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
- Gene Name
- rpoB
- Uniprot ID
- Q8RQE9
- Uniprot Name
- DNA-directed RNA polymerase subunit beta
- Molecular Weight
- 125263.41 Da
References
- Vassylyev DG, Svetlov V, Vassylyeva MN, Perederina A, Igarashi N, Matsugaki N, Wakatsuki S, Artsimovitch I: Structural basis for transcription inhibition by tagetitoxin. Nat Struct Mol Biol. 2005 Dec;12(12):1086-93. Epub 2005 Nov 6. [Article]
- Kind
- Protein
- Organism
- Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
- Pharmacological action
- Unknown
- General Function
- Dna-directed rna polymerase activity
- Specific Function
- DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
- Gene Name
- rpoC
- Uniprot ID
- Q8RQE8
- Uniprot Name
- DNA-directed RNA polymerase subunit beta'
- Molecular Weight
- 170755.075 Da
References
- Vassylyev DG, Svetlov V, Vassylyeva MN, Perederina A, Igarashi N, Matsugaki N, Wakatsuki S, Artsimovitch I: Structural basis for transcription inhibition by tagetitoxin. Nat Struct Mol Biol. 2005 Dec;12(12):1086-93. Epub 2005 Nov 6. [Article]
Drug created at September 11, 2007 17:49 / Updated at June 12, 2020 16:52