You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameIxabepilone
Accession NumberDB04845
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionIxabepilone is an epothilone B analog developed by Bristol-Myers Squibb as a cancer drug. On October 16, 2007, the U.S. Food and Drug Administration approved ixabepilone for the treatment of aggressive metastatic or locally advanced breast cancer no longer responding to currently available chemotherapies. Ixabepilone is administered through injection, and will be marketed under the trade name Ixempra. Ixabepilone is a semisynthetic analogue of epothilone B. It has a lactone–lactam modification that minimizes susceptibility to esterase degradation.
Structure
Thumb
Synonyms
Aza-epothilone B
Azaepothilone B
External Identifiers
  • BMS 247550-01
  • BMS-247550
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
IxemprakitE.R. Squibb & Sons, L.L.C.2007-10-16Not applicableUs
IxemprakitE.R. Squibb & Sons, L.L.C.2007-10-16Not applicableUs
IxemprakitR Pharm Us Operating, Llc2007-10-16Not applicableUs
IxemprakitR Pharm Us Operating, Llc2007-10-16Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIK27005NP0A
CAS number219989-84-1
WeightAverage: 506.7
Monoisotopic: 506.281443634
Chemical FormulaC27H42N2O5S
InChI KeyFABUFPQFXZVHFB-PVYNADRNSA-N
InChI
InChI=1S/C27H42N2O5S/c1-15-9-8-10-27(7)22(34-27)12-20(16(2)11-19-14-35-18(4)28-19)29-23(31)13-21(30)26(5,6)25(33)17(3)24(15)32/h11,14-15,17,20-22,24,30,32H,8-10,12-13H2,1-7H3,(H,29,31)/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]-17-oxa-4-azabicyclo[14.1.0]heptadecane-5,9-dione
SMILES
[H][C@]12C[[email protected]](NC(=O)C[[email protected]](O)C(C)(C)C(=O)[[email protected]](C)[C@@H](O)[C@@H](C)CCC[C@@]1(C)O2)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
  • Macrolactam
  • 2,4-disubstituted 1,3-thiazole
  • Azole
  • Heteroaromatic compound
  • Thiazole
  • Carboxamide group
  • Ketone
  • Lactam
  • Cyclic ketone
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Carboxylic acid derivative
  • Dialkyl ether
  • Oxirane
  • Ether
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Alcohol
  • Organic oxygen compound
  • Carbonyl group
  • Organic oxide
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationInvestigated for use/treatment in breast cancer, head and neck cancer, melanoma, lung cancer, lymphoma (non-hodgkin's), prostate cancer, renal cell carcinoma, and cancer/tumors (unspecified).
PharmacodynamicsNot Available
Mechanism of actionBinding of Ixabepilone to beta-tubulins (e.g. beta-III tubulin) stabilizes microtubules. Microtubules are essential to cell division, and epothilones therefore stop cells from properly dividing. Like taxol, Ixabepilone binds to the αβ-tubulin heterodimer subunit. Once bound, the rate of αβ-tubulin dissociation decreases, thus stabilizing the microtubules.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding67-77%
MetabolismNot Available
Route of eliminationMostly fecal and some renal.
Half life52 hours
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+0.7027
Blood Brain Barrier-0.7665
Caco-2 permeable-0.6495
P-glycoprotein substrateSubstrate0.7622
P-glycoprotein inhibitor INon-inhibitor0.7441
P-glycoprotein inhibitor IINon-inhibitor0.9149
Renal organic cation transporterNon-inhibitor0.9214
CYP450 2C9 substrateNon-substrate0.8138
CYP450 2D6 substrateNon-substrate0.8112
CYP450 3A4 substrateSubstrate0.6367
CYP450 1A2 substrateNon-inhibitor0.6554
CYP450 2C9 inhibitorNon-inhibitor0.7055
CYP450 2D6 inhibitorNon-inhibitor0.9011
CYP450 2C19 inhibitorNon-inhibitor0.6097
CYP450 3A4 inhibitorNon-inhibitor0.7629
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7608
Ames testNon AMES toxic0.604
CarcinogenicityNon-carcinogens0.9028
BiodegradationNot ready biodegradable0.8001
Rat acute toxicity2.6638 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9957
hERG inhibition (predictor II)Non-inhibitor0.8922
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Kit
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6605599 No1998-05-262018-05-26Us
US6670384 Yes2002-07-232022-07-23Us
US7022330 Yes2002-07-232022-07-23Us
US7125899 Yes1998-11-262018-11-26Us
US7312237 Yes2005-02-212025-02-21Us
USRE41393 Yes2002-08-082022-08-08Us
USRE41911 Yes2001-03-282021-03-28Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00352 mg/mLALOGPS
logP3.28ALOGPS
logP3.39ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)13.85ChemAxon
pKa (Strongest Basic)2.73ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area112.05 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity136.71 m3·mol-1ChemAxon
Polarizability56.86 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Ismat Ullah, Gary Wiley, “Enteric coated bead comprising ixabepilone, and preparation and administration thereof.” U.S. Patent US20060153917, issued July 13, 2006.

US20060153917
General ReferencesNot Available
External Links
ATC CodesL01DC04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Ixabepilone.
AmiodaroneThe serum concentration of Ixabepilone can be increased when it is combined with Amiodarone.
AprepitantThe serum concentration of Ixabepilone can be increased when it is combined with Aprepitant.
AtazanavirThe serum concentration of Ixabepilone can be increased when it is combined with Atazanavir.
AtomoxetineThe metabolism of Ixabepilone can be decreased when combined with Atomoxetine.
BevacizumabBevacizumab may increase the cardiotoxic activities of Ixabepilone.
BexaroteneThe serum concentration of Ixabepilone can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Ixabepilone can be increased when it is combined with Boceprevir.
BortezomibThe metabolism of Ixabepilone can be decreased when combined with Bortezomib.
BosentanThe serum concentration of Ixabepilone can be decreased when it is combined with Bosentan.
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Ixabepilone.
CarbamazepineThe serum concentration of Ixabepilone can be decreased when it is combined with Carbamazepine.
CeritinibThe serum concentration of Ixabepilone can be increased when it is combined with Ceritinib.
ClarithromycinThe serum concentration of Ixabepilone can be increased when it is combined with Clarithromycin.
ClemastineThe metabolism of Ixabepilone can be decreased when combined with Clemastine.
ClotrimazoleThe metabolism of Ixabepilone can be decreased when combined with Clotrimazole.
ClozapineThe risk or severity of adverse effects can be increased when Ixabepilone is combined with Clozapine.
CobicistatThe serum concentration of Ixabepilone can be increased when it is combined with Cobicistat.
ConivaptanThe serum concentration of Ixabepilone can be increased when it is combined with Conivaptan.
CrizotinibThe metabolism of Ixabepilone can be decreased when combined with Crizotinib.
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Ixabepilone.
CyclosporineThe metabolism of Ixabepilone can be decreased when combined with Cyclosporine.
DabrafenibThe serum concentration of Ixabepilone can be decreased when it is combined with Dabrafenib.
DarunavirThe serum concentration of Ixabepilone can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Ixabepilone can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Ixabepilone can be decreased when it is combined with Deferasirox.
DelavirdineThe metabolism of Ixabepilone can be decreased when combined with Delavirdine.
DeslanosideDeslanoside may decrease the cardiotoxic activities of Ixabepilone.
DexamethasoneThe serum concentration of Ixabepilone can be decreased when it is combined with Dexamethasone.
DigitoxinDigitoxin may decrease the cardiotoxic activities of Ixabepilone.
DigoxinDigoxin may decrease the cardiotoxic activities of Ixabepilone.
DihydroergotamineThe metabolism of Ixabepilone can be decreased when combined with Dihydroergotamine.
DiltiazemThe metabolism of Ixabepilone can be decreased when combined with Diltiazem.
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Ixabepilone.
DoxycyclineThe metabolism of Ixabepilone can be decreased when combined with Doxycycline.
DronedaroneThe metabolism of Ixabepilone can be decreased when combined with Dronedarone.
EfavirenzThe serum concentration of Ixabepilone can be decreased when it is combined with Efavirenz.
EnzalutamideThe serum concentration of Ixabepilone can be decreased when it is combined with Enzalutamide.
ErythromycinThe metabolism of Ixabepilone can be decreased when combined with Erythromycin.
Eslicarbazepine acetateThe serum concentration of Ixabepilone can be decreased when it is combined with Eslicarbazepine acetate.
EtravirineThe serum concentration of Ixabepilone can be decreased when it is combined with Etravirine.
FluconazoleThe metabolism of Ixabepilone can be decreased when combined with Fluconazole.
FluvoxamineThe metabolism of Ixabepilone can be decreased when combined with Fluvoxamine.
FosamprenavirThe metabolism of Ixabepilone can be decreased when combined with Fosamprenavir.
FosaprepitantThe serum concentration of Ixabepilone can be increased when it is combined with Fosaprepitant.
FosphenytoinThe serum concentration of Ixabepilone can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Ixabepilone can be increased when it is combined with Fusidic Acid.
IdelalisibThe serum concentration of Ixabepilone can be increased when it is combined with Idelalisib.
ImatinibThe metabolism of Ixabepilone can be decreased when combined with Imatinib.
IndinavirThe serum concentration of Ixabepilone can be increased when it is combined with Indinavir.
IsavuconazoniumThe metabolism of Ixabepilone can be decreased when combined with Isavuconazonium.
IsradipineThe metabolism of Ixabepilone can be decreased when combined with Isradipine.
ItraconazoleThe serum concentration of Ixabepilone can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Ixabepilone can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Ixabepilone can be increased when it is combined with Ketoconazole.
LopinavirThe serum concentration of Ixabepilone can be increased when it is combined with Lopinavir.
LovastatinThe metabolism of Ixabepilone can be decreased when combined with Lovastatin.
LuliconazoleThe serum concentration of Ixabepilone can be increased when it is combined with Luliconazole.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Ixabepilone.
MifepristoneThe metabolism of Ixabepilone can be decreased when combined with Mifepristone.
MitotaneThe serum concentration of Ixabepilone can be decreased when it is combined with Mitotane.
ModafinilThe serum concentration of Ixabepilone can be decreased when it is combined with Modafinil.
NafcillinThe serum concentration of Ixabepilone can be decreased when it is combined with Nafcillin.
NefazodoneThe serum concentration of Ixabepilone can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Ixabepilone can be increased when it is combined with Nelfinavir.
NetupitantThe serum concentration of Ixabepilone can be increased when it is combined with Netupitant.
NevirapineThe metabolism of Ixabepilone can be decreased when combined with Nevirapine.
NilotinibThe metabolism of Ixabepilone can be decreased when combined with Nilotinib.
OlaparibThe metabolism of Ixabepilone can be decreased when combined with Olaparib.
OsimertinibThe serum concentration of Ixabepilone can be increased when it is combined with Osimertinib.
OuabainOuabain may decrease the cardiotoxic activities of Ixabepilone.
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Ixabepilone.
PalbociclibThe serum concentration of Ixabepilone can be increased when it is combined with Palbociclib.
PentobarbitalThe serum concentration of Ixabepilone can be decreased when it is combined with Pentobarbital.
PhenobarbitalThe serum concentration of Ixabepilone can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Ixabepilone can be decreased when it is combined with Phenytoin.
PosaconazoleThe serum concentration of Ixabepilone can be increased when it is combined with Posaconazole.
PrimidoneThe serum concentration of Ixabepilone can be decreased when it is combined with Primidone.
RanolazineThe metabolism of Ixabepilone can be decreased when combined with Ranolazine.
RifabutinThe serum concentration of Ixabepilone can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Ixabepilone can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Ixabepilone can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Ixabepilone can be increased when it is combined with Ritonavir.
SaquinavirThe serum concentration of Ixabepilone can be increased when it is combined with Saquinavir.
SildenafilThe metabolism of Ixabepilone can be decreased when combined with Sildenafil.
SiltuximabThe serum concentration of Ixabepilone can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Ixabepilone can be increased when it is combined with Simeprevir.
St. John's WortThe serum concentration of Ixabepilone can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Ixabepilone can be increased when it is combined with Stiripentol.
SulfisoxazoleThe metabolism of Ixabepilone can be decreased when combined with Sulfisoxazole.
TelaprevirThe serum concentration of Ixabepilone can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Ixabepilone can be increased when it is combined with Telithromycin.
TiclopidineThe metabolism of Ixabepilone can be decreased when combined with Ticlopidine.
TocilizumabThe serum concentration of Ixabepilone can be decreased when it is combined with Tocilizumab.
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Ixabepilone.
VenlafaxineThe metabolism of Ixabepilone can be decreased when combined with Venlafaxine.
VerapamilThe metabolism of Ixabepilone can be decreased when combined with Verapamil.
VoriconazoleThe serum concentration of Ixabepilone can be increased when it is combined with Voriconazole.
ZiprasidoneThe metabolism of Ixabepilone can be decreased when combined with Ziprasidone.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
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 critical role in proper axon guidance and mantainance.
Gene Name:
TUBB3
Uniprot ID:
Q13509
Molecular Weight:
50432.355 Da
References
  1. Vahdat L: Ixabepilone: a novel antineoplastic agent with low susceptibility to multiple tumor resistance mechanisms. Oncologist. 2008 Mar;13(3):214-21. doi: 10.1634/theoncologist.2007-0167. [PubMed:18378531 ]
  2. Denduluri N, Swain SM: Ixabepilone for the treatment of solid tumors: a review of clinical data. Expert Opin Investig Drugs. 2008 Mar;17(3):423-35. doi: 10.1517/13543784.17.3.423 . [PubMed:18321240 ]
  3. Goodin S: Ixabepilone: a novel microtubule-stabilizing agent for the treatment of metastatic breast cancer. Am J Health Syst Pharm. 2008 Nov 1;65(21):2017-26. doi: 10.2146/ajhp070628. [PubMed:18945860 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Goel S, Cohen M, Comezoglu SN, Perrin L, Andre F, Jayabalan D, Iacono L, Comprelli A, Ly VT, Zhang D, Xu C, Humphreys WG, McDaid H, Goldberg G, Horwitz SB, Mani S: The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of ixabepilone: a first in class epothilone B analogue in late-phase clinical development. Clin Cancer Res. 2008 May 1;14(9):2701-9. doi: 10.1158/1078-0432.CCR-07-4151. [PubMed:18451235 ]
Comments
comments powered by Disqus
Drug created on October 16, 2007 16:43 / Updated on October 01, 2016 03:35