Epothilone D

Identification

Name
Epothilone D
Accession Number
DB01873  (EXPT01350)
Type
Small Molecule
Groups
Experimental, Investigational
Description
Not Available
Structure
Thumb
Synonyms
  • (-)-desoxyepothilone B
  • 12,13-desoxyepothilone B
  • Desoxyepothilone B
External IDs
KOS-862 / NSC-703147 / R-1492 / R1492
Categories
UNII
T0358E0YUF
CAS number
189453-10-9
Weight
Average: 491.683
Monoisotopic: 491.270544117
Chemical Formula
C27H41NO5S
InChI Key
XOZIUKBZLSUILX-GIQCAXHBSA-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
(4S,7R,8S,9S,13Z,16S)-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
[H]\C(=C(\C)[[email protected]]1([H])C\C([H])=C(C)/CCC[[email protected]]([H])(C)[[email protected]]([H])(O)[[email protected]@]([H])(C)C(=O)C(C)(C)[[email protected]@]([H])(O)CC(=O)O1)C1=CSC(C)=N1

Pharmacology

Indication

Investigated for use/treatment in colorectal cancer, lung cancer, breast cancer, solid tumors, and prostate cancer.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

The 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.

TargetActionsOrganism
UTubulin alpha-3C/D chainNot AvailableHuman
UTubulin beta chainNot AvailableHuman
UTubulin beta-1 chainNot AvailableHuman
UTubulin beta-4B chainNot AvailableHuman
UTubulin beta-4A chainNot AvailableHuman
UTubulin alpha-4A chainNot AvailableHuman
UTubulin beta-3 chainNot AvailableHuman
UTubulin alpha-1C chainNot AvailableHuman
UTubulin alpha-8 chainNot AvailableHuman
UTubulin alpha-1B chainNot AvailableHuman
UTubulin alpha-1A chainNot AvailableHuman
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

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 References
Not Available
External Links
KEGG Compound
C12039
PubChem Compound
447865
PubChem Substance
46508361
ChemSpider
9400674
ChEBI
29579
ChEMBL
CHEMBL96172
HET
EPD
Wikipedia
Epothilone
PDB Entries
1pkf

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentNeoplasms1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentLung Cancers1
2TerminatedTreatmentLung Cancers1
2TerminatedTreatmentProstate Cancer1

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 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
Polarizability55.09 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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 inhibitorNon-inhibitor0.7697
CYP450 2D6 inhibitorNon-inhibitor0.92
CYP450 2C19 inhibitorNon-inhibitor0.612
CYP450 3A4 inhibitorNon-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
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 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.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Macrolides and analogues
Sub Class
Epothilones and analogues
Direct Parent
Epothilones and analogues
Alternative Parents
2,4-disubstituted thiazoles / Heteroaromatic compounds / Secondary alcohols / Lactones / Cyclic ketones / Carboxylic acid esters / Oxacyclic compounds / Monocarboxylic acids and derivatives / Azacyclic compounds / Organopnictogen compounds
show 3 more
Substituents
Epothilone / 2,4-disubstituted 1,3-thiazole / Azole / Heteroaromatic compound / Thiazole / Carboxylic acid ester / Ketone / Lactone / Secondary alcohol / Cyclic ketone
show 15 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Macrolides and lactone polyketides (C12039) / Macrolides and lactone polyketides (LMPK04000001)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Structural constituent of cytoskeleton
Specific Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Gene Name
TUBA3C
Uniprot ID
Q13748
Uniprot Name
Tubulin alpha-3C/D chain
Molecular Weight
49959.145 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Ubiquitin protein ligase binding
Specific Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Gene Name
TUBB
Uniprot ID
P07437
Uniprot Name
Tubulin beta chain
Molecular Weight
49670.515 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Structural constituent of cytoskeleton
Specific Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
Gene Name
TUBB1
Uniprot ID
Q9H4B7
Uniprot Name
Tubulin beta-1 chain
Molecular Weight
50326.56 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Unfolded protein binding
Specific Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Gene Name
TUBB4B
Uniprot ID
P68371
Uniprot Name
Tubulin beta-4B chain
Molecular Weight
49830.72 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Structural constituent of cytoskeleton
Specific Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Gene Name
TUBB4A
Uniprot ID
P04350
Uniprot Name
Tubulin beta-4A chain
Molecular Weight
49585.475 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Structural constituent of cytoskeleton
Specific Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Gene Name
TUBA4A
Uniprot ID
P68366
Uniprot Name
Tubulin alpha-4A chain
Molecular Weight
49923.995 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Structural constituent of cytoskeleton
Specific Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. TUBB3 plays a criti...
Gene Name
TUBB3
Uniprot ID
Q13509
Uniprot Name
Tubulin beta-3 chain
Molecular Weight
50432.355 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Structural molecule activity
Specific Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Gene Name
TUBA1C
Uniprot ID
Q9BQE3
Uniprot Name
Tubulin alpha-1C chain
Molecular Weight
49894.93 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Specific Function
Gtp binding
Gene Name
TUBA8
Uniprot ID
Q9NY65
Uniprot Name
Tubulin alpha-8 chain
Molecular Weight
50093.12 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Ubiquitin protein ligase binding
Specific Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Gene Name
TUBA1B
Uniprot ID
P68363
Uniprot Name
Tubulin alpha-1B chain
Molecular Weight
50151.24 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Specific Function
Gtp binding
Gene Name
TUBA1A
Uniprot ID
Q71U36
Uniprot Name
Tubulin alpha-1A chain
Molecular Weight
50135.25 Da
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:17139284]
  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:17016423]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 14:49