Identification

Name
Ixabepilone
Accession Number
DB04845
Description

Ixabepilone is an epothilone B analog developed by Bristol-Myers Squibb as a cancer drug. It was FDA approved on October 16, 2007, for the treatment of unresponsive aggressive metastatic or locally advanced breast cancer. 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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 506.7
Monoisotopic: 506.281443634
Chemical Formula
C27H42N2O5S
Synonyms
  • Aza-epothilone B
  • Azaepothilone B
  • Ixabepilone
External IDs
  • BMS 247550-01
  • BMS-247550

Pharmacology

Indication

Investigated 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).

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics
Not Available
Mechanism of action

Binding 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.

TargetActionsOrganism
ATubulin beta-3 chain
inhibitor
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

67-77%

Metabolism
Not Available
Route of elimination

Mostly fecal and some renal.

Half-life

52 hours

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Ixabepilone can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Ixabepilone can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Ixabepilone.
AcalabrutinibThe metabolism of Ixabepilone can be decreased when combined with Acalabrutinib.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Ixabepilone.
AcetaminophenThe metabolism of Ixabepilone can be increased when combined with Acetaminophen.
AcetazolamideThe metabolism of Ixabepilone can be decreased when combined with Acetazolamide.
AcetyldigitoxinThe serum concentration of Acetyldigitoxin can be increased when it is combined with Ixabepilone.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Ixabepilone.
AdalimumabThe metabolism of Ixabepilone can be increased when combined with Adalimumab.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid grapefruit products. Grapefruit inhibits the CYP3A4 metabolism of ixabepilone, which may increase its serum concentration.
  • Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of ixabepilone.

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IxempraKit45 mg/45mgIntravenousE.R. Squibb & Sons, L.L.C.2007-10-162017-10-31US flag
IxempraKit45 mg/45mgIntravenousR-Pharm US Operating, LLC2007-10-16Not applicableUS flag
IxempraKit15 mg/15mgIntravenousE.R. Squibb & Sons, L.L.C.2007-10-162017-10-31US flag
Ixempra15 mg/15mgIntravenousR-Pharm US Operating, LLC2007-10-16Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L01DC04 — Ixabepilone
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Macrolactams / 2,4-disubstituted thiazoles / Heteroaromatic compounds / Secondary carboxylic acid amides / Secondary alcohols / Lactams / Cyclic ketones / Oxacyclic compounds / Epoxides / Dialkyl ethers
show 5 more
Substituents
2,4-disubstituted 1,3-thiazole / Alcohol / Aromatic heteropolycyclic compound / Azacycle / Azole / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Cyclic ketone / Dialkyl ether
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
epoxide, 1,3-thiazole, lactam, beta-hydroxy ketone, macrocycle (CHEBI:63605)

Chemical Identifiers

UNII
K27005NP0A
CAS number
219989-84-1
InChI Key
FABUFPQFXZVHFB-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][[email protected]]12C[[email protected]](NC(=O)C[[email protected]](O)C(C)(C)C(=O)[[email protected]](C)[[email protected]@H](O)[[email protected]@H](C)CCC[[email protected]@]1(C)O2)C(\C)=C\C1=CSC(C)=N1

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 References
  1. FDA Approved Drug Products: Ixempra (ixabepilone) kit for intravenous infusion [Link]
KEGG Drug
D04645
PubChem Compound
6445540
PubChem Substance
99443224
ChemSpider
20145579
RxNav
337523
ChEBI
63605
ChEMBL
CHEMBL1201752
ZINC
ZINC000003993846
PharmGKB
PA165958343
Wikipedia
Ixabepilone

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentBreast Cancer1
3Active Not RecruitingTreatmentEstrogen Receptor Negative / Estrogen Receptor Positive / HER2/Neu Negative / HER2/Neu Positive / Progesterone Receptor Negative / Progesterone Receptor Positive / Recurrent Breast Carcinoma / Stage IIIC Breast Cancer AJCC v6 / Stage IV Breast Cancer AJCC v6 and v71
3CompletedTreatmentBreast Cancer1
3CompletedTreatmentBreast Cancer / Malignancies1
3CompletedTreatmentBreast Cancer / Metastases1
3CompletedTreatmentBreast Cancer / Metastasis1
3TerminatedSupportive CareNeuropathies / Pain / Recurrent Breast Carcinoma / Stage IV Breast Cancer1
3TerminatedTreatmentEndometrial Cancer1
2Active Not RecruitingTreatmentBilateral Breast Carcinoma / HER2/Neu Negative / Invasive Breast Carcinoma1
2Active Not RecruitingTreatmentEndometrial Adenocarcinomas / Endometrial Adenosquamous Carcinoma / Endometrial Clear Cell Adenocarcinoma / Endometrial Serous Adenocarcinoma / Recurrent Uterine Corpus Cancer / Stage IIIA Uterine Corpus Cancer AJCC v7 / Stage IIIB Uterine Corpus Cancer AJCC v7 / Stage IIIC Uterine Corpus Cancer AJCC v7 / Stage IVA Uterine Corpus Cancer AJCC v7 / Stage IVB Uterine Corpus Cancer AJCC v71

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solution15 mg
Injection, powder, for solution45 mg
KitIntravenous15 mg/15mg
KitIntravenous45 mg/45mg
Injection, powder, lyophilized, for solutionIntravenous15 mg
Injection, powder, lyophilized, for solutionIntravenous45 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6605599No2003-08-122018-05-26US flag
US6670384Yes2003-12-302022-07-23US flag
US7022330Yes2006-04-042022-07-23US flag
US7125899Yes2006-10-242018-11-26US flag
US7312237Yes2007-12-252025-02-21US flag
USRE41393Yes2010-06-222022-08-08US flag
USRE41911Yes2010-11-022021-03-28US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
Not 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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

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

Targets

Kind
Protein
Organism
Humans
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 criti...
Gene Name
TUBB3
Uniprot ID
Q13509
Uniprot Name
Tubulin beta-3 chain
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
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
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]
  2. Kuper JI, D'Aprile M: Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease. Clin Pharmacokinet. 2000 Sep;39(3):203-14. doi: 10.2165/00003088-200039030-00003. [PubMed:11020135]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. FDA Approved Drug Products: Ixempra (ixabepilone) kit for intravenous infusion [Link]

Drug created on October 16, 2007 16:43 / Updated on July 04, 2020 01:15

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