Patupilone

Identification

Name
Patupilone
Accession Number
DB03010  (EXPT01349)
Type
Small Molecule
Groups
Experimental, Investigational
Description

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

Structure
Thumb
Synonyms
  • (−)-epothilone B
  • Epo B
  • Epothilone B
External IDs
EPO 906 / EPO 906A / EPO-906 / EPO-906A
Categories
UNII
UEC0H0URSE
CAS number
152044-54-7
Weight
Average: 507.683
Monoisotopic: 507.265458739
Chemical Formula
C27H41NO6S
InChI Key
QXRSDHAAWVKZLJ-PVYNADRNSA-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,7S,10R,11S,12S,16R)-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
[H]\C(=C(\C)[[email protected]]1([H])C[[email protected]]2([H])O[[email protected]]2(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 ovarian cancer, lung cancer, brain cancer, breast cancer, and gastric 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. 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.

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
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Patupilone.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Patupilone.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of Patupilone.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Patupilone.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Patupilone.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Patupilone.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Patupilone.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Patupilone.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Patupilone.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Patupilone.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Patupilone.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Patupilone.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Patupilone.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Patupilone.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Patupilone.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Patupilone.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Patupilone.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Patupilone.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Patupilone.Approved, Investigational
Food Interactions
Not 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 References
Not Available
External Links
KEGG Compound
C12154
PubChem Compound
448013
PubChem Substance
46505629
ChemSpider
10213816
ChEBI
31550
ChEMBL
CHEMBL94657
Therapeutic Targets Database
DNC000616
HET
EPB
PDB Entries
1q5d

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAdvanced Malignancies1
1CompletedTreatmentAdvanced Malignancies / Tumors2
1CompletedTreatmentAdvanced Malignancies / Tumors, Solid1
1CompletedTreatmentAdvanced Solid Tumors1
1CompletedTreatmentCentral Nervous System Neoplasms / Neoplasms, Head and Neck1
1CompletedTreatmentMalignant Neoplasm of Colon1
1CompletedTreatmentRefractory Malignancy1
1CompletedTreatmentTumors1
1CompletedTreatmentTumors, Solid1
1TerminatedTreatmentAdvanced Malignancies1
1WithdrawnTreatmentTumors, Solid1
1, 2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2CompletedTreatmentRecurrent Glioblastoma Planned for Reoperation1
2CompletedTreatmentAbdominal wall neoplasm / Fallopian Tube Neoplasms / Neoplasms, Ovarian1
2CompletedTreatmentBrain Metastasis / Lung Cancer Non-Small Cell Cancer (NSCLC)1
2CompletedTreatmentCancer, Breast / Metastatic Cancers1
2CompletedTreatmentCarcinoids / Neuroendocrine Tumors1
2CompletedTreatmentColonic Neoplasms / Neoplasms, Colorectal1
2CompletedTreatmentHepatocellular,Carcinoma1
2CompletedTreatmentHormone Refractory Prostate Cancer1
2CompletedTreatmentMelanoma1
2CompletedTreatmentMetastatic Hormone Refractory Prostate Cancer1
2CompletedTreatmentNeoplasms, Breast1
2CompletedTreatmentNeoplasms, Kidney1
2CompletedTreatmentProstatic Neoplasms1
3CompletedTreatmentAbdominal wall neoplasm / Cancer, Ovarian / Fallopian Tube 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 Solubility0.00342 mg/mLALOGPS
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
Polarizability56.11 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8471
Blood Brain Barrier+0.6791
Caco-2 permeable-0.5935
P-glycoprotein substrateSubstrate0.7384
P-glycoprotein inhibitor INon-inhibitor0.8232
P-glycoprotein inhibitor IINon-inhibitor0.9779
Renal organic cation transporterNon-inhibitor0.9193
CYP450 2C9 substrateNon-substrate0.84
CYP450 2D6 substrateNon-substrate0.8309
CYP450 3A4 substrateSubstrate0.622
CYP450 1A2 substrateInhibitor0.5065
CYP450 2C9 inhibitorNon-inhibitor0.7468
CYP450 2D6 inhibitorNon-inhibitor0.9114
CYP450 2C19 inhibitorNon-inhibitor0.6114
CYP450 3A4 inhibitorNon-inhibitor0.7163
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8841
Ames testNon AMES toxic0.5816
CarcinogenicityNon-carcinogens0.933
BiodegradationReady biodegradable0.5
Rat acute toxicity2.7983 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9924
hERG inhibition (predictor II)Non-inhibitor0.935
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 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 / Epoxides / Dialkyl ethers
show 5 more
Substituents
Epothilone / 2,4-disubstituted 1,3-thiazole / Azole / Heteroaromatic compound / Thiazole / Carboxylic acid ester / Ketone / Lactone / Secondary alcohol / Cyclic ketone
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
1,3-thiazole, oxabicycloalkane (CHEBI:42432) / Macrolides and lactone polyketides (C12154) / Macrolides and lactone polyketides (LMPK04000041)

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 November 09, 2017 03:22