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Identification
NameEpothilone D
Accession NumberDB01873  (EXPT01350)
TypeSmall Molecule
GroupsExperimental, Investigational
DescriptionNot Available
Structure
Thumb
Synonyms
SynonymLanguageCode
KOS-862Not AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
CAS number189453-10-9
WeightAverage: 491.683
Monoisotopic: 491.270544117
Chemical FormulaC27H41NO5S
InChI KeyXOZIUKBZLSUILX-UKMAFROXSA-N
InChI
InChI=1S/C27H41NO5S/c1-16-9-8-10-17(2)25(31)19(4)26(32)27(6,7)23(29)14-24(30)33-22(12-11-16)18(3)13-21-15-34-20(5)28-21/h11,13,15,17,19,22-23,25,29,31H,8-10,12,14H2,1-7H3/b16-11-,18-13+/t17-,19-,22+,23+,25+/m0/s1
IUPAC Name
(4R,7S,8R,9S,13Z,16R)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-[(1E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-1-oxacyclohexadec-13-ene-2,6-dione
SMILES
C[C@H]1CCC\C(C)=C/C[C@@H](OC(=O)C[C@@H](O)C(C)(C)C(=O)[C@@H](C)[C@@H]1O)C(\C)=C\C1=CSC(C)=N1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as epothilones and analogues. These are macrolides consisting of a 16-member lactone ring conjugated at the carbon 16 with a 1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl group. Some epothilone analogues containing a lactam ring instead of the lactone ring.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassMacrolides and analogues
Sub ClassEpothilones and analogues
Direct ParentEpothilones and analogues
Alternative Parents
Substituents
  • Epothilone
  • 2,4-disubstituted 1,3-thiazole
  • Heteroaromatic compound
  • Thiazole
  • Azole
  • Cyclic ketone
  • Secondary alcohol
  • Lactone
  • Ketone
  • Carboxylic acid ester
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationInvestigated for use/treatment in colorectal cancer, lung cancer, breast cancer, solid tumors, and prostate cancer.
PharmacodynamicsNot Available
Mechanism of actionThe principal mechanism of the epothilone class is inhibition of microtubule function. Microtubules are essential to cell division, and epothilones therefore stop cells from properly dividing.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8749
Blood Brain Barrier+0.7345
Caco-2 permeable-0.5948
P-glycoprotein substrateSubstrate0.689
P-glycoprotein inhibitor INon-inhibitor0.8151
P-glycoprotein inhibitor IINon-inhibitor0.9518
Renal organic cation transporterNon-inhibitor0.9136
CYP450 2C9 substrateNon-substrate0.8473
CYP450 2D6 substrateNon-substrate0.8372
CYP450 3A4 substrateSubstrate0.6028
CYP450 1A2 substrateNon-inhibitor0.5443
CYP450 2C9 substrateNon-inhibitor0.7697
CYP450 2D6 substrateNon-inhibitor0.92
CYP450 2C19 substrateNon-inhibitor0.612
CYP450 3A4 substrateNon-inhibitor0.835
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8559
Ames testNon AMES toxic0.6843
CarcinogenicityNon-carcinogens0.9367
BiodegradationNot ready biodegradable0.5931
Rat acute toxicity2.8243 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9905
hERG inhibition (predictor II)Non-inhibitor0.9322
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00246 mg/mLALOGPS
logP4.54ALOGPS
logP5.1ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)14.09ChemAxon
pKa (Strongest Basic)2.73ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area96.72 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity136.04 m3·mol-1ChemAxon
Polarizability55.11 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Ludger Wessjohann, “Epothilone synthesis building blocks III and IV: asymmetrically substituted acyloins and acyloin derivatives, methods for their production and methods for the production of epothilones B, D and epothilone derivatives.” U.S. Patent US20040082651, issued April 29, 2004.

US20040082651
General ReferenceNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Tubulin alpha-3C/D chain

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Tubulin alpha-3C/D chain Q13748 Details

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
  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

2. Tubulin beta chain

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Tubulin beta chain P07437 Details

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
  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

3. Tubulin beta-1 chain

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Tubulin beta-1 chain Q9H4B7 Details

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
  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

4. Tubulin beta-4B chain

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Tubulin beta-4B chain P68371 Details

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
  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

5. Tubulin beta-4A chain

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Tubulin beta-4A chain P04350 Details

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
  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

6. Tubulin alpha-4A chain

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Tubulin alpha-4A chain P68366 Details

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
  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

7. Tubulin beta-3 chain

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Tubulin beta-3 chain Q13509 Details

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
  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

8. Tubulin alpha-1C chain

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Tubulin alpha-1C chain Q9BQE3 Details

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
  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

9. Tubulin alpha-8 chain

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Tubulin alpha-8 chain Q9NY65 Details

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
  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

10. Tubulin alpha-1B chain

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Tubulin alpha-1B chain P68363 Details

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
  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

11. Tubulin alpha-1A chain

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Tubulin alpha-1A chain Q71U36 Details

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
  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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:16