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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
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).
Structured Indications
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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Tubulin beta-3 chainProteinyes
inhibitor
HumanQ13509 details
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
Interactions
Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Ixabepilone.Approved
AmiodaroneThe serum concentration of Ixabepilone can be increased when it is combined with Amiodarone.Approved, Investigational
AnvirzelAnvirzel may decrease the cardiotoxic activities of Ixabepilone.Investigational
AprepitantThe serum concentration of Ixabepilone can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe serum concentration of Ixabepilone can be increased when it is combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Ixabepilone can be decreased when combined with Atomoxetine.Approved
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Ixabepilone.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Ixabepilone.Approved, Investigational
BexaroteneThe serum concentration of Ixabepilone can be decreased when it is combined with Bexarotene.Approved, Investigational
BoceprevirThe serum concentration of Ixabepilone can be increased when it is combined with Boceprevir.Approved
BortezomibThe metabolism of Ixabepilone can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Ixabepilone can be decreased when it is combined with Bosentan.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Ixabepilone.Approved
CarbamazepineThe serum concentration of Ixabepilone can be decreased when it is combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Ixabepilone can be increased when it is combined with Ceritinib.Approved
ClarithromycinThe serum concentration of Ixabepilone can be increased when it is combined with Clarithromycin.Approved
ClemastineThe metabolism of Ixabepilone can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Ixabepilone can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Ixabepilone is combined with Clozapine.Approved
CobicistatThe serum concentration of Ixabepilone can be increased when it is combined with Cobicistat.Approved
ConivaptanThe serum concentration of Ixabepilone can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Ixabepilone can be decreased when combined with Crizotinib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Ixabepilone.Approved, Investigational
CyclosporineThe metabolism of Ixabepilone can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Ixabepilone can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe serum concentration of Ixabepilone can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Ixabepilone can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Ixabepilone can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Ixabepilone can be decreased when combined with Delavirdine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Ixabepilone.Approved
DexamethasoneThe serum concentration of Ixabepilone can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Ixabepilone.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Ixabepilone.Approved
DihydroergotamineThe metabolism of Ixabepilone can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Ixabepilone can be decreased when combined with Diltiazem.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Ixabepilone.Approved, Investigational
DoxycyclineThe metabolism of Ixabepilone can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Ixabepilone can be decreased when combined with Dronedarone.Approved
EfavirenzThe serum concentration of Ixabepilone can be decreased when it is combined with Efavirenz.Approved, Investigational
EnzalutamideThe serum concentration of Ixabepilone can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Ixabepilone can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe serum concentration of Ixabepilone can be decreased when it is combined with Eslicarbazepine acetate.Approved
EtravirineThe serum concentration of Ixabepilone can be decreased when it is combined with Etravirine.Approved
FluconazoleThe metabolism of Ixabepilone can be decreased when combined with Fluconazole.Approved
FluvoxamineThe metabolism of Ixabepilone can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Ixabepilone can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Ixabepilone can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe serum concentration of Ixabepilone can be decreased when it is combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Ixabepilone can be increased when it is combined with Fusidic Acid.Approved
IdelalisibThe serum concentration of Ixabepilone can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Ixabepilone can be decreased when combined with Imatinib.Approved
IndinavirThe serum concentration of Ixabepilone can be increased when it is combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Ixabepilone can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Ixabepilone can be decreased when combined with Isradipine.Approved
ItraconazoleThe serum concentration of Ixabepilone can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Ixabepilone can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe serum concentration of Ixabepilone can be increased when it is combined with Ketoconazole.Approved, Investigational
LopinavirThe serum concentration of Ixabepilone can be increased when it is combined with Lopinavir.Approved
LovastatinThe metabolism of Ixabepilone can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Ixabepilone can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Ixabepilone can be decreased when it is combined with Lumacaftor.Approved
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Ixabepilone.Withdrawn
MifepristoneThe serum concentration of Ixabepilone can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Ixabepilone can be decreased when it is combined with Mitotane.Approved
ModafinilThe serum concentration of Ixabepilone can be decreased when it is combined with Modafinil.Approved, Investigational
NafcillinThe serum concentration of Ixabepilone can be decreased when it is combined with Nafcillin.Approved
NefazodoneThe serum concentration of Ixabepilone can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Ixabepilone can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Ixabepilone can be increased when it is combined with Netupitant.Approved
NevirapineThe serum concentration of Ixabepilone can be decreased when it is combined with Nevirapine.Approved
NilotinibThe metabolism of Ixabepilone can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Ixabepilone can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Ixabepilone can be increased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Ixabepilone.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Ixabepilone.Approved, Vet Approved
PalbociclibThe serum concentration of Ixabepilone can be increased when it is combined with Palbociclib.Approved
PentobarbitalThe serum concentration of Ixabepilone can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe serum concentration of Ixabepilone can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Ixabepilone can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe serum concentration of Ixabepilone can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe serum concentration of Ixabepilone can be decreased when it is combined with Primidone.Approved, Vet Approved
RanolazineThe metabolism of Ixabepilone can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe serum concentration of Ixabepilone can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Ixabepilone can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Ixabepilone can be decreased when it is combined with Rifapentine.Approved
RitonavirThe serum concentration of Ixabepilone can be increased when it is combined with Ritonavir.Approved, Investigational
SaquinavirThe serum concentration of Ixabepilone can be increased when it is combined with Saquinavir.Approved, Investigational
SildenafilThe metabolism of Ixabepilone can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Ixabepilone can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Ixabepilone can be increased when it is combined with Simeprevir.Approved
St. John's WortThe serum concentration of Ixabepilone can be decreased when it is combined with St. John's Wort.Nutraceutical
StiripentolThe serum concentration of Ixabepilone can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Ixabepilone can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe serum concentration of Ixabepilone can be increased when it is combined with Telaprevir.Approved
TelithromycinThe serum concentration of Ixabepilone can be increased when it is combined with Telithromycin.Approved
TiclopidineThe metabolism of Ixabepilone can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Ixabepilone can be decreased when it is combined with Tocilizumab.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Ixabepilone.Approved, Investigational
VenlafaxineThe metabolism of Ixabepilone can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Ixabepilone can be decreased when combined with Verapamil.Approved
VoriconazoleThe serum concentration of Ixabepilone can be increased when it is combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Ixabepilone can be decreased when combined with Ziprasidone.Approved
Food InteractionsNot 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
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
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

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
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Drug created on October 16, 2007 16:43 / Updated on December 07, 2016 03:54