Identification
NameIxabepilone
Accession NumberDB04845
TypeSmall Molecule
GroupsApproved, Investigational
Description

Ixabepilone 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 IDs BMS 247550-01 / BMS-247550
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
IxempraKitE.R. Squibb & Sons, L.L.C.2007-10-16Not applicableUs
IxempraKitR Pharm Us Operating, Llc2007-10-16Not applicableUs
IxempraKitE.R. Squibb & Sons, L.L.C.2007-10-16Not 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
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
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).

Structured Indications
PharmacodynamicsNot 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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Tubulin beta-3 chainProteinyes
inhibitor
HumanQ13509 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding

67-77%

MetabolismNot Available
Route of elimination

Mostly fecal and some renal.

Half life

52 hours

ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not 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
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
BCG vaccineThe 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.Withdrawn
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
OleandrinAnvirzel may decrease the cardiotoxic activities of Ixabepilone.Experimental
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.Withdrawn
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 — Ixabepilone
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentAdult Solid Neoplasm1
1Active Not RecruitingTreatmentCancer, Breast1
1Active Not RecruitingTreatmentMale Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
1CompletedTreatmentAdvanced Solid Tumors / Neoplasms2
1CompletedTreatmentBrain and Central Nervous System Tumors / Cancer, Ovarian / Childhood Germ Cell Tumor / Extragonadal Germ Cell Tumor / Leukemias / Liver Cancer / Neuroblastomas / Renal Cancers / Sarcomas / Unspecified Childhood Solid Tumor, Protocol Specific1
1CompletedTreatmentCancer, Advanced1
1CompletedTreatmentCancer, Breast2
1CompletedTreatmentCancer, Breast / Cancer, Ovarian / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentCancers1
1CompletedTreatmentMalignant Lymphomas / Small Intestine Cancer / Unspecified Adult Solid Tumor, Protocol Specific2
1CompletedTreatmentMetastatic Breast Cancer (MBC)1
1CompletedTreatmentNeutropenias / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)2
1CompletedTreatmentSolid Malignancies1
1CompletedTreatmentTumors, Solid2
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific3
1TerminatedPreventionCancer, Breast / Head and Neck Carcinoma / Hepatocellular Cancer / Lung Cancers / Malignant Neoplasm of Colon / Malignant Neoplasm of Pancreas / Renal Cancers / Sarcomas1
1TerminatedTreatmentAdvanced Solid Tumors1
1TerminatedTreatmentLocally Advanced or Metastatic Breast Cancer1
1TerminatedTreatmentUnspecified Adult Solid Tumor, Protocol Specific2
1Unknown StatusTreatmentRecurrent Endometrial Cancer1
1WithdrawnTreatmentAdvanced Solid Tumors1
1, 2CompletedTreatmentAdenocarcinoma of the Prostate / Recurrent Prostate Cancer / Stage IV Prostate Cancer1
1, 2CompletedTreatmentAdult Anaplastic Astrocytoma / Adult Giant Cell Glioblastoma / Adult Gliosarcoma / Recurrent Adult Brain Tumor1
1, 2CompletedTreatmentCancers1
1, 2CompletedTreatmentFallopian Tube Cancer / Female Reproductive Cancer / Recurrent Breast Cancer / Recurrent Ovarian Epithelial Cancer / Stage III Ovarian Epithelial Cancer / Stage IV Breast Cancer / Stage IV Ovarian Epithelial Cancer1
1, 2CompletedTreatmentHead and Neck Carcinoma1
1, 2CompletedTreatmentMalignant Neoplasm of Prostate1
1, 2CompletedTreatmentMetastatic Breast Cancer (MBC)2
1, 2TerminatedTreatmentCancer, Breast1
1, 2Unknown StatusTreatmentMalignant Neoplasm of Prostate1
1, 2Unknown StatusTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1, 2WithdrawnTreatmentCancer, Breast / Metastatic Breast Cancer (MBC) / Stage IV Breast Cancer1
2Active Not RecruitingTreatmentCancer, Breast2
2Active Not RecruitingTreatmentEndometrial Adenocarcinomas / Endometrial Adenosquamous Carcinoma / Endometrial Clear Cell Adenocarcinoma / Endometrial Serous Adenocarcinoma / Recurrent Uterine Corpus Carcinoma / Stage IIIA Uterine Corpus Cancer / Stage IIIB Uterine Corpus Cancer / Stage IIIC Uterine Corpus Cancer / Stage IVA Uterine Corpus Cancer / Stage IVB Uterine Corpus Cancer1
2Active Not RecruitingTreatmentRecurrent Uterine Corpus Sarcoma / Uterine Corpus Leiomyosarcoma1
2Active Not RecruitingTreatmentRecurrent Uterine Sarcoma / Uterine Carcinosarcoma1
2CompletedTreatmentAdenocarcinoma of the Cervix / Adenosquamous carcinoma of the cervix / Cervical Carcinoma / Cervical Carcinoma, Non-SquamousType1
2CompletedTreatmentAdenocarcinoma of the Prostate / Recurrent Prostate Cancer / Stage IV Prostate Cancer2
2CompletedTreatmentAdult Rhabdomyosarcoma / Adult Synovial Sarcoma / Alveolar Childhood Rhabdomyosarcoma / Childhood Synovial Sarcoma / Embryonal Childhood Rhabdomyosarcoma / Previously Treated Childhood Rhabdomyosarcoma / Recurrent Adult Soft Tissue Sarcoma / Recurrent Childhood Rhabdomyosarcoma / Recurrent Childhood Soft Tissue Sarcoma / Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Recurrent Neuroblastoma / Recurrent Osteosarcoma / Recurrent Wilms Tumor and Other Childhood Kidney Tumors1
2CompletedTreatmentAdvanced/Metastatic Non-Small Cell Lung Cancer1
2CompletedTreatmentAnaplastic Large Cell Lymphoma / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma1
2CompletedTreatmentBrain and Central Nervous System Tumors / Cancer, Ovarian / Extragonadal Germ Cell Tumor / Testicular germ cell tumour1
2CompletedTreatmentCancer, Breast7
2CompletedTreatmentCancer, Breast / Metastases1
2CompletedTreatmentClear Cell Renal Cell Carcinoma / Recurrent Renal Cell Cancer / Stage III Renal Cell Cancer / Stage IV Renal Cell Cancer1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentDistal Urethral Cancer / Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter / Proximal Urethral Cancer / Recurrent Bladder Cancer / Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter / Recurrent Urethral Cancer / Regional Transitional Cell Cancer of the Renal Pelvis and Ureter / Stage III Bladder Cancer / Stage IV Bladder Cancer / Transitional Cell Carcinoma of the Bladder / Urethral Cancer Associated With Invasive Bladder Cancer1
2CompletedTreatmentEndometrial Adenocarcinomas / Recurrent Endometrial Carcinoma / Stage IV Endometrial Carcinoma1
2CompletedTreatmentEsophageal Cancers / Malignant Neoplasm of Stomach2
2CompletedTreatmentHER2-positive Breast Cancer / Male Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
2CompletedTreatmentLeukemias / Malignant Lymphomas1
2CompletedTreatmentMalignant Neoplasm of Pancreas1
2CompletedTreatmentMalignant Neoplasm of Prostate2
2CompletedTreatmentMetastatic Breast Cancer (MBC)7
2CompletedTreatmentMetastatic Breast Cancer (MBC) / Triple Negative Locally Advanced Non-resectable Breast Cancer1
2CompletedTreatmentMetastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma / Recurrent Metastatic Squamous Neck Cancer With Occult Primary / Recurrent Salivary Gland Cancer / Recurrent Squamous Cell Carcinoma of the Hypopharynx / Recurrent Squamous Cell Carcinoma of the Larynx / Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity / Recurrent Squamous Cell Carcinoma of the Oropharynx / Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Recurrent Verrucous Carcinoma of the Larynx / Recurrent Verrucous Carcinoma of the Oral Cavity / Salivary Gland Squamous Cell Carcinoma / Stage IV Squamous Cell Carcinoma of the Hypopharynx / Stage IVA Salivary Gland Cancer / Stage IVA Squamous Cell Carcinoma of the Larynx / Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVA Squamous Cell Carcinoma of the Oropharynx / Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IVA Verrucous Carcinoma of the Larynx / Stage IVA Verrucous Carcinoma of the Oral Cavity / Stage IVB Salivary Gland Cancer / Stage IVB Squamous Cell Carcinoma of the Larynx / Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVB Squamous Cell Carcinoma of the Oropharynx / Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IVB Verrucous Carcinoma of the Larynx / Stage IVB Verrucous Carcinoma of the Oral Cavity / Stage IVC Salivary Gland Cancer / Stage IVC Squamous Cell Carcinoma of the Larynx / Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVC Squamous Cell Carcinoma of the Oropharynx / Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IVC Verrucous Carcinoma of the Larynx / Stage IVC Verrucous Carcinoma of the Oral Cavity / Tongue Cancer1
2CompletedTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)1
2CompletedTreatmentPancreatic Cancer Metastatic1
2CompletedTreatmentPrimary Peritoneal Cavity Cancer / Recurrent Ovarian Epithelial Cancer1
2CompletedTreatmentRecurrent Melanoma / Stage IV Melanoma1
2CompletedTreatmentRenal Cell Adenocarcinoma2
2CompletedTreatmentStomach Neoplasms1
2RecruitingTreatmentCancer, Breast / Neoplasms, Breast1
2RecruitingTreatmentFallopian Tube Cancer / Ovarian Epithelial Cancer / Primary Peritoneal Cancer1
2TerminatedTreatmentAdenocarcinomas / Carcinoma NOS / Genital Diseases, Male / Genital Neoplasms, Male / Genitourinary tract neoplasm / Neoplasms, Glandular and Epithelial / Prostatic Diseases / Prostatic Neoplasms1
2TerminatedTreatmentAdult Primary Cholangiocellular Carcinoma / Adult Primary Hepatocellular Carcinoma / Advanced Adult Primary Liver Cancer / Cholangiocarcinoma of the Extrahepatic Bile Duct / Cholangiocarcinoma of the Gallbladder / Localized Extrahepatic Bile Duct Cancer / Localized Gallbladder Cancer / Localized Resectable Adult Primary Liver Cancer / Localized Unresectable Adult Primary Liver Cancer / Recurrent Adult Primary Liver Cancer / Recurrent Extrahepatic Bile Duct Cancer / Recurrent Gallbladder Cancer / Unresectable Extrahepatic Bile Duct Cancer / Unresectable Gallbladder Cancer1
2TerminatedTreatmentCancer, Breast1
2TerminatedTreatmentColorectal Cancers1
2TerminatedTreatmentHER2-positive Breast Cancer / Recurrent Breast Cancer / Stage IV Breast Cancer1
2TerminatedTreatmentMetastatic Breast Cancer (MBC)2
2TerminatedTreatmentNeoplasms, Breast1
2TerminatedTreatmentNon-Squamous Non-Small Cell Lung Cancer1
2TerminatedTreatmentRecurrent Adult Soft Tissue Sarcoma / Stage III Adult Soft Tissue Sarcoma / Stage IV Adult Soft Tissue Sarcoma1
2Unknown StatusTreatmentCancer, Ovarian / Peritoneal Cavity Cancer1
2Unknown StatusTreatmentMetastatic Breast Cancer (MBC)1
2WithdrawnTreatmentLung Cancers1
3Active Not RecruitingTreatmentCancer, Breast2
3Active Not RecruitingTreatmentEstrogen Receptor Negative / Estrogen Receptor Positive / HER2/Neu Negative / HER2/Neu Positive / Male Breast Carcinoma / Progesterone Receptor Negative / Progesterone Receptor Positive / Recurrent Breast Carcinoma / Stage IIIC Breast Cancer AJCC v6 / Stage IV Breast Cancer1
3CompletedTreatmentCancer, Breast / Cancers1
3CompletedTreatmentCancer, Breast / Metastases1
3RecruitingTreatmentCancer, Breast / Metastasis1
3TerminatedSupportive CareNeuropathy / Pain / Recurrent Breast Carcinoma / Stage IV Breast Cancer1
3TerminatedTreatmentEndometrial Cancers1
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 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
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot 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 ParentsMacrolactams / 2,4-disubstituted thiazoles / Heteroaromatic compounds / Secondary carboxylic acid amides / Secondary alcohols / Lactams / Cyclic ketones / Oxacyclic compounds / Epoxides / Dialkyl ethers
SubstituentsEpothilone / Macrolactam / 2,4-disubstituted 1,3-thiazole / Azole / Heteroaromatic compound / Thiazole / Carboxamide group / Ketone / Lactam / Cyclic ketone
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptorsepoxide, 1,3-thiazole, lactam, beta-hydroxy ketone, macrocycle (CHEBI:63605 )

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
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
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
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 ]
Drug created on October 16, 2007 16:43 / Updated on July 27, 2017 16:03