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Identification
NameEpothilone B
Accession NumberDB03010  (EXPT01349)
TypeSmall Molecule
GroupsExperimental, Investigational
Description

Epothilone B is a 16-membered macrolide that mimics the biological effects of taxol.

Structure
Thumb
Synonyms
SynonymLanguageCode
EPO 906Not AvailableNot Available
EPO906Not AvailableNot Available
patupiloneNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
Categories
CAS number152044-54-7
WeightAverage: 507.683
Monoisotopic: 507.265458739
Chemical FormulaC27H41NO6S
InChI KeyQXRSDHAAWVKZLJ-TYFQHMATSA-N
InChI
InChI=1S/C27H41NO6S/c1-15-9-8-10-27(7)22(34-27)12-20(16(2)11-19-14-35-18(4)28-19)33-23(30)13-21(29)26(5,6)25(32)17(3)24(15)31/h11,14-15,17,20-22,24,29,31H,8-10,12-13H2,1-7H3/b16-11+/t15-,17-,20-,21+,22-,24+,27-/m0/s1
IUPAC Name
(1S,3S,7R,10S,11R,12S,16S)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[(1E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione
SMILES
C[C@H]1CCC[C@]2(C)O[C@H]2C[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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassPhenylpropanoids and Polyketides
ClassMacrolides and Analogues
SubclassEpothilones and Analogues
Direct parentEpothilones and Analogues
Alternative parentsDiterpenes; 2,4-disubstituted Thiazoles; Secondary Alcohols; Ketones; Carboxylic Acid Esters; Polyamines; Epoxides; Ethers
Substituentsditerpene; 2,4-disubstituted 1,3-thiazole; thiazole; azole; secondary alcohol; carboxylic acid ester; ketone; polyamine; carboxylic acid derivative; ether; oxirane; organonitrogen compound; alcohol; carbonyl group
Classification descriptionThis compound belongs to the 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.
Pharmacology
IndicationInvestigated for use/treatment in ovarian cancer, lung cancer, brain cancer, breast cancer, and gastric 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. Epothilone B possess the same biological effects as taxol both in vitro and in cultured cells. This is because they share the same binding site, as well as binding affinity to the microtubule. Like taxol, epothilone B binds to the αβ-tubulin heterodimer subunit. Once bound, the rate of αβ-tubulin dissociation decreases, thus stabilizing the microtubules. Furthermore, epothilone B has also been shown to induce tubulin polymerization into microtubules without the presence of GTP. This is caused by formation of microtubule bundles throughout the cytoplasm. Finally, epothilone B also causes cell cycle arrest at the G2-M transition phase, thus leading to cytotoxicity and eventually cell apoptosis.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.8471
Blood Brain Barrier + 0.6791
Caco-2 permeable - 0.5935
P-glycoprotein substrate Substrate 0.7384
P-glycoprotein inhibitor I Non-inhibitor 0.8232
P-glycoprotein inhibitor II Non-inhibitor 0.9779
Renal organic cation transporter Non-inhibitor 0.9193
CYP450 2C9 substrate Non-substrate 0.84
CYP450 2D6 substrate Non-substrate 0.8309
CYP450 3A4 substrate Substrate 0.622
CYP450 1A2 substrate Inhibitor 0.5065
CYP450 2C9 substrate Non-inhibitor 0.7468
CYP450 2D6 substrate Non-inhibitor 0.9114
CYP450 2C19 substrate Non-inhibitor 0.6114
CYP450 3A4 substrate Non-inhibitor 0.7163
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8841
Ames test Non AMES toxic 0.5816
Carcinogenicity Non-carcinogens 0.933
Biodegradation Ready biodegradable 0.5
Rat acute toxicity 2.7983 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9924
hERG inhibition (predictor II) Non-inhibitor 0.935
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00342ALOGPS
logP3.7ALOGPS
logP4.12ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)14.09ChemAxon
pKa (Strongest Basic)2.73ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area109.25 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity134.76 m3·mol-1ChemAxon
Polarizability56.64 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Richard Taylor, “Derivatives of epothilone B and D and synthesis thereof.” U.S. Patent US20030176473, issued September 18, 2003.

US20030176473
General ReferenceNot Available
External Links
ResourceLink
PubChem Compound46936553
PubChem Substance46505629
Therapeutic Targets DatabaseDNC000616
HETEPB
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 17:19