Tagetitoxin

Identification

Name
Tagetitoxin
Accession Number
DB04788
Type
Small Molecule
Groups
Experimental
Description

Tagetitoxin is a bacterial phytotoxin. It preferentially inhibits eukaryotic RNA polymerase.

Structure
Thumb
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
Categories
UNII
Not Available
CAS number
87913-21-1
Weight
Average: 416.298
Monoisotopic: 416.029066598
Chemical Formula
C11H17N2O11PS
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
CC(=O)O[C@@H]1[C@H](N)[C@@H](OP(O)(O)=O)[C@]2(CS[C@](O)([C@@H]1O2)C(N)=O)C(O)=O

Pharmacology

Indication
Not Available
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.

TargetActionsOrganism
UDNA-directed RNA polymerase subunit betaNot AvailableThermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
UDNA-directed RNA polymerase subunit beta'Not AvailableThermus 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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Plet JR, Porter MJ: Synthesis of the bicyclic core of tagetitoxin. Chem Commun (Camb). 2006 Mar 21;(11):1197-9. Epub 2006 Feb 14. [PubMed:16518489]
  2. 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. [PubMed:16273103]
  3. Mathews DE, Durbin RD: Mechanistic aspects of tagetitoxin inhibition of RNA polymerase from Escherichia coli. Biochemistry. 1994 Oct 4;33(39):11987-92. [PubMed:7918417]
  4. 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. [PubMed:2403565]
External Links
PubChem Compound
5327077
PubChem Substance
46506068
ChemSpider
4484333
HET
TGT
Wikipedia
Tagetitoxin
PDB Entries
2be5

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 Solubility37.5 mg/mLALOGPS
logP-1.5ALOGPS
logP-3.8ChemAxon
logS-1ALOGPS
pKa (Strongest Acidic)0.85ChemAxon
pKa (Strongest Basic)8.72ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area228.93 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity80.58 m3·mol-1ChemAxon
Polarizability34.14 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9526
Blood Brain Barrier-0.8728
Caco-2 permeable-0.678
P-glycoprotein substrateNon-substrate0.5244
P-glycoprotein inhibitor INon-inhibitor0.755
P-glycoprotein inhibitor IINon-inhibitor1.0
Renal organic cation transporterNon-inhibitor0.9637
CYP450 2C9 substrateNon-substrate0.6653
CYP450 2D6 substrateNon-substrate0.8187
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.7787
CYP450 2C9 inhibitorNon-inhibitor0.8173
CYP450 2D6 inhibitorNon-inhibitor0.9095
CYP450 2C19 inhibitorNon-inhibitor0.793
CYP450 3A4 inhibitorNon-inhibitor0.892
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9468
Ames testNon AMES toxic0.5863
CarcinogenicityNon-carcinogens0.9072
BiodegradationNot ready biodegradable0.9783
Rat acute toxicity2.5607 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9967
hERG inhibition (predictor II)Non-inhibitor0.8383
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 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
Delta amino acid or derivatives / Gamma amino acid or derivatives / Monoalkyl phosphate / Dicarboxylic acid or derivatives / Monosaccharide / Organic phosphoric acid derivative / Oxane / 1,4-oxathiane / Phosphoric acid ester / Pyran
show 22 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

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
  1. 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. [PubMed:16273103]
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
  1. 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. [PubMed:16273103]

Drug created on September 11, 2007 11:49 / Updated on November 02, 2018 06:05