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Identification
- Summary
Ixabepilone is a microtubule inhibitor administered in combination with capecitabine or alone in the treatment of metastatic or locally advanced breast cancer that has shown inadequate response to taxanes and anthracyclines.
- Brand Names
- Ixempra
- Generic Name
- Ixabepilone
- DrugBank Accession Number
- DB04845
- Background
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
Structure for Ixabepilone (DB04845)
- 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).
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Locally advanced breast cancer Regimen in combination with: Capecitabine (DB01101) •••••••••••• Treatment of Locally advanced breast cancer •••••••••••• Used in combination to treat Metastatic breast cancer Regimen in combination with: Capecitabine (DB01101) •••••••••••• Treatment of Metastatic breast cancer •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism ATubulin beta-3 chain inhibitorHumans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Ixabepilone can be increased when it is combined with Abametapir. Abatacept The metabolism of Ixabepilone can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Ixabepilone. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Ixabepilone. Acalabrutinib The metabolism of Ixabepilone can be decreased when combined with Acalabrutinib. - 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
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ixempra Injection, solution; Kit 15 mg/15mg Intravenous R-Pharm US Operating, LLC 2007-10-16 Not applicable US 
Ixempra Kit 45 mg/45mg Intravenous E.R. Squibb & Sons, L.L.C. 2007-10-16 2017-10-31 US Ixempra Kit 45 mg/45mg Intravenous R-Pharm US Operating, LLC 2007-10-16 Not applicable US Ixempra Kit 15 mg/15mg Intravenous E.R. Squibb & Sons, L.L.C. 2007-10-16 2017-10-31 US
Categories
- ATC Codes
- L01DC04 — Ixabepilone
- Drug Categories
- Anti-Bacterial Agents
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Substrates
- Cytotoxic Antibiotics and Related Substances
- Immunosuppressive Agents
- Lactones
- Macrolides
- Microtubule Inhibition
- Microtubule Inhibitors
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Polyketides
- Tubulin Modulators
- 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)
- Affected organisms
- Not Available
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][C@]12C[C@H](NC(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC[C@@]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
- FDA Approved Drug Products: Ixempra (ixabepilone) kit for intravenous infusion [Link]
- External Links
- KEGG Drug
- D04645
- PubChem Compound
- 6445540
- PubChem Substance
- 99443224
- ChemSpider
- 20145579
- 337523
- ChEBI
- 63605
- ChEMBL
- CHEMBL1201752
- ZINC
- ZINC000003993846
- PharmGKB
- PA165958343
- PDBe Ligand
- GZX
- Wikipedia
- Ixabepilone
- PDB Entries
- 7daf
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Terminated Not Available Breast Cancer / Breast Neoplasms 1 somestatus stop reason just information to hide Not Available Unknown Status Not Available Breast Cancer Organoids 1 somestatus stop reason just information to hide 3 Completed Treatment Breast Cancer 2 somestatus stop reason just information to hide 3 Completed Treatment Breast Cancer / Cancer 1 somestatus stop reason just information to hide 3 Completed Treatment Breast Cancer / Metastatic Cancer 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution; kit Intravenous 15 mg/15mg Kit Intravenous 15 mg/15mg Kit Intravenous 45 mg/45mg Injection, powder, for solution 15 mg/1vial Injection, powder, lyophilized, for solution Intravenous 15 mg Injection, powder, lyophilized, for solution Intravenous 45 mg Solution Parenteral 15.000 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6605599 No 2003-08-12 2018-05-26 US US6670384 Yes 2003-12-30 2022-07-23 US US7022330 Yes 2006-04-04 2022-07-23 US US7125899 Yes 2006-10-24 2018-11-26 US US7312237 Yes 2007-12-25 2025-02-21 US USRE41393 Yes 2010-06-22 2022-08-08 US USRE41911 Yes 2010-11-02 2021-03-28 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00352 mg/mL ALOGPS logP 3.28 ALOGPS logP 3.39 Chemaxon logS -5.2 ALOGPS pKa (Strongest Acidic) 13.85 Chemaxon pKa (Strongest Basic) 2.73 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 112.05 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 136.71 m3·mol-1 Chemaxon Polarizability 56.86 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.7027 Blood Brain Barrier - 0.7665 Caco-2 permeable - 0.6495 P-glycoprotein substrate Substrate 0.7622 P-glycoprotein inhibitor I Non-inhibitor 0.7441 P-glycoprotein inhibitor II Non-inhibitor 0.9149 Renal organic cation transporter Non-inhibitor 0.9214 CYP450 2C9 substrate Non-substrate 0.8138 CYP450 2D6 substrate Non-substrate 0.8112 CYP450 3A4 substrate Substrate 0.6367 CYP450 1A2 substrate Non-inhibitor 0.6554 CYP450 2C9 inhibitor Non-inhibitor 0.7055 CYP450 2D6 inhibitor Non-inhibitor 0.9011 CYP450 2C19 inhibitor Non-inhibitor 0.6097 CYP450 3A4 inhibitor Non-inhibitor 0.7629 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7608 Ames test Non AMES toxic 0.604 Carcinogenicity Non-carcinogens 0.9028 Biodegradation Not ready biodegradable 0.8001 Rat acute toxicity 2.6638 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9957 hERG inhibition (predictor II) Non-inhibitor 0.8922
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 224.7272232 predictedDarkChem Lite v0.1.0 [M-H]- 230.01163 predictedDeepCCS 1.0 (2019) [M+H]+ 225.3120232 predictedDarkChem Lite v0.1.0 [M+H]+ 231.90704 predictedDeepCCS 1.0 (2019) [M+Na]+ 225.0458232 predictedDarkChem Lite v0.1.0 [M+Na]+ 237.54872 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers (PubMed:34996871). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms (PubMed:34996871). Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin (PubMed:34996871). TUBB3 plays a critical role in proper axon guidance and maintenance (PubMed:20074521). Binding of NTN1/Netrin-1 to its receptor UNC5C might cause dissociation of UNC5C from polymerized TUBB3 in microtubules and thereby lead to increased microtubule dynamics and axon repulsion (PubMed:28483977). Plays a role in dorsal root ganglion axon projection towards the spinal cord (PubMed:28483977)
- Specific Function
- GTP binding
- Gene Name
- TUBB3
- Uniprot ID
- Q13509
- Uniprot Name
- Tubulin beta-3 chain
- Molecular Weight
- 50432.355 Da
References
- 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. [Article]
- 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 . [Article]
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- 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. [Article]
- 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. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- FDA Approved Drug Products: Ixempra (ixabepilone) kit for intravenous infusion [Link]
Drug created at October 16, 2007 22:43 / Updated at February 21, 2021 18:51