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Ixabepilone

July 24, 2017
Common Name

Ixabepilone 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. [Wikipedia] Ixabepilone is a semisynthetic analogue of epothilone B. It has a lactone lactam modification that Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source Aza-epothilone bHMDB Azaepothilone bHMDB BMS-247550HMDB

Chemical Formlia

C27H42N2O5S Average Molecliar Weight

506.698 Monoisotopic Molecliar Weight

506.281443154 IUPAC Name

(1S,3S,7R,10S,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 Traditional Name

ixempra CAS Registry Number

219989-84-1 SMILES

C[C@H]1CCC[C@@]2(C)O[C@@]2([H])C[C@H](NC(=O)C[C@@H](O)C(C)(C)C(=O)[C@@H](C)[C@H]1O)C(C)=CC1=CSC(C)=N1

InChI Identifier

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

InChI Key

FABUFPQFXZVHFB-CFWQTKTJSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities 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

Chemical entities Super Class

Organic compounds Class

Phenylpropanoids and polyketides Sub Class

Macrolides 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
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organonitrogen compounds
  • Organic oxides
  • Hydrocarbon derivatives

    • Substituents

  • Epothilone
  • Macrolactam
  • 2,4-disubstituted 1,3-thiazole
  • Azole
  • Heteroaromatic compound
  • Thiazole
  • Carboxamide group
  • Ketone
  • Lactam
  • Secondary alcohol
  • Cyclic ketone
  • Secondary carboxylic acid amide
  • Carboxylic acid derivative
  • Dialkyl ether
  • Oxirane
  • Ether
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Organic oxide
  • Alcohol
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Carbonyl group
  • Organopnictogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

    Not Available Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Antineoplastic Agents

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility3.52e-03 g/LNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility0.0035 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 Polarizability57.06 Å3ChemAxon Number of Rings3ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Cytoplasm
  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB04845

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB04845

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB04845 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    4949236 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Ixabepilone NuGOwiki Link

    HMDB15593 Metagene Link

    HMDB15593 METLIN ID

    Not Available PubChem Compound

    23305354 PDB ID

    Not Available ChEBI ID

    Not Available

    Product: Clinafloxacin

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References Not Available

    Enzymes

    General function:
    Involved in monooxygenase 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 xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
    Gene Name:
    CYP3A4
    Uniprot ID:
    P08684
    Molecular weight:
    57255.585
    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 ]
    General function:
    Involved in structural molecule activity
    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:
    50432.4
    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 ]

    PMID: 11672565

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