ixabepilone 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
1517 219989-84-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • ixabepilone
  • Azaepothilone B
  • ixempra
  • BMS-247550
Ixabepilone is a semi-synthetic analog of epothilone B. Ixabepilone binds directly to beta-tubulin subunits on microtubules, leading to suppression of microtubule dynamics. Ixabepilone suppresses the dynamic instability of alphaBeta-II and alphaBeta-III microtubules. Ixabepilone possesses low in vitro susceptibility to multiple tumor resistance mechanisms including efflux transporters, such as MRP-1 and P-glycoprotein (P-gp). Ixabepilone blocks cells in the mitotic phase of the cell division cycle, leading to cell death.
  • Molecular weight: 506.70
  • Formula: C27H42N2O5S
  • CLOGP: 3.67
  • LIPINSKI: 1
  • HAC: 7
  • HDO: 3
  • TPSA: 112.05
  • ALOGS: -5.16
  • ROTB: 2
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 5.60 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 1.97 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution) 11 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 10 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.20 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 17 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.690 Moderate 0.77
caco2-efflux Caco-2 efflux ratio (BA/AB) 4.457 Moderate 0.77
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 38.905 10^-6 cm/s Moderate 0.77
dh-clint Dog hepatocyte intrinsic clearance 12.503 uL/min/10^6 cells Moderate 0.77
dppb Dog plasma protein binding (% unbound) 21.670 % Moderate 0.77
fcs-ppb Fetal calf serum protein binding (% unbound) 37.920 % Moderate 0.77
herg hERG pIC50 4.284 pIC50 Moderate 0.77
hh-clint Human hepatocyte intrinsic clearance 3.090 uL/min/10^6 cells Moderate 0.77
hlm-clint Human liver microsomal intrinsic clearance 48.306 uL/min/mg protein Moderate 0.77
hppb Human plasma protein binding (% unbound) 29.090 % Moderate 0.77
kinase-safety-class ACVR2B,CAMK2D,CDK5,EIF2AK3,GRK2,ITK,PDK1,PDK2,PRKDC 9
kinase-selectivity-class GRK2 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 15.996 Moderate 0.77
mh-clint Mouse hepatocyte intrinsic clearance 18.793 Moderate 0.77
mppb Mouse plasma protein binding (% unbound) 23.730 Moderate 0.77
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 56.494 Moderate 0.77
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 30.830 % Moderate 0.77
rh-clint Rat hepatocyte intrinsic clearance 26.669 uL/min/10^6 cells Moderate 0.77
rh-fuinc Rat hepatocyte fraction unbound in incubation 67.630 % Moderate 0.77
rppb Rat plasma protein binding (% unbound) 24.530 % Moderate 0.77
solubility-dd Solubility at pH 7.4 in DMSO 683.912 uM Moderate 0.77

Approvals:

DateAgencyCompanyOrphan
Oct. 16, 2007 FDA BRISTOL MYERS SQUIBB

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Pseudocirrhosis 190.87 41.06 30 1814 914 90625689
Neutrophil count decreased 132.51 41.06 51 1793 71481 90555122
Portal hypertension 97.86 41.06 22 1822 4679 90621924
White blood cell count decreased 91.13 41.06 51 1793 167058 90459545
Anaemia 81.88 41.06 63 1781 352739 90273864
Neutropenia 69.91 41.06 48 1796 224856 90401747
Platelet count decreased 51.60 41.06 33 1811 136936 90489667
Malignant neoplasm progression 51.12 41.06 30 1814 106840 90519763
Dehydration 49.97 41.06 37 1807 194410 90432193
Disease progression 49.94 41.06 34 1810 156581 90470022
Febrile neutropenia 49.60 41.06 34 1810 158315 90468288

FDA Adverse Event Reporting System (Male)

None

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Pseudocirrhosis 188.96 38.85 28 1434 895 110586942
Neutrophil count decreased 128.03 38.85 51 1411 120890 110466947
White blood cell count decreased 105.43 38.85 54 1408 229336 110358501
Portal hypertension 88.77 38.85 21 1441 8616 110579221
Anaemia 70.88 38.85 58 1404 547028 110040809
Neutropenia 51.06 38.85 41 1421 374579 110213258
Platelet count decreased 48.98 38.85 33 1429 230410 110357427
Malignant neoplasm progression 41.93 38.85 27 1435 174540 110413297
Febrile neutropenia 39.60 38.85 33 1429 316734 110271103

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01DC04 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
CYTOTOXIC ANTIBIOTICS AND RELATED SUBSTANCES
Other cytotoxic antibiotics
FDA PE N0000175085 Microtubule Inhibition
FDA EPC N0000175592 Microtubule Inhibitor
CHEBI has role CHEBI:22587 antiviral agent
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:61951 microtubule-destabilising agent

Related Drugs by ATC class:

L01DC Other cytotoxic antibiotics 3 drugs
bleomycinmitomycinplicamycin

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Carcinoma of breast indication 254838004 DOID:3459
Metastatic Breast Carcinoma indication
Hyperbilirubinemia contraindication 14783006 DOID:2741
Conduction disorder of the heart contraindication 44808001
Heart disease contraindication 56265001 DOID:114
Hepatic failure contraindication 59927004
Acute infectious disease contraindication 63171007
Diabetes mellitus contraindication 73211009 DOID:9351
Liver function tests abnormal contraindication 166603001
Disease of liver contraindication 235856003 DOID:409
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Peripheral nerve disease contraindication 302226006
Neutropenic disorder contraindication 303011007 DOID:1227
Breastfeeding (mother) contraindication 413712001
Myocardial ischemia contraindication 414795007 DOID:3393




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.56 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Tubulin beta Tumour-associated antigen INHIBITOR SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Apoptosis regulator Bcl-2 Cytosolic other Kd 6.47 CHEMBL

External reference:

IDSource
4026737 VUID
N0000179767 NUI
D04645 KEGG_DRUG
4026737 VANDF
C1135132 UMLSCUI
CHEBI:63605 CHEBI
GZX PDB_CHEM_ID
CHEMBL1201752 ChEMBL_ID
DB04845 DRUGBANK_ID
C430592 MESH_SUPPLEMENTAL_RECORD_UI
6824 IUPHAR_LIGAND_ID
8390 INN_ID
K27005NP0A UNII
6445540 PUBCHEM_CID
337523 RXNORM
121505 MMSL
24628 MMSL
d07051 MMSL
012371 NDDF
428282007 SNOMEDCT_US
429022006 SNOMEDCT_US
K27005NP0A INXIGHT DRUGS

Pharmaceutical products:

None