Ixabepilone

Ixabepilone (INN; also known as azaepothilone B, codenamed BMS-247550) is a pharmaceutical drug developed by Bristol-Myers Squibb as a chemotherapeutic medication for cancer.[1]

Ixabepilone
Clinical data
Trade namesIxempra
Other namesAzaepothilone B
AHFS/Drugs.comMonograph
MedlinePlusa608042
License data
Routes of
administration		Intravenous infusion
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityN/A
Protein binding67 to 77%
MetabolismExtensive, hepatic, CYP3A4-mediated
Elimination half-life52 hours
ExcretionFecal (mostly) and renal
Identifiers
IUPAC name
  • (1R,5S,6S,7R,10S,14S,16S)-6,10-dihydroxy-1,5,7,
    9,9-pentamethyl-14-[(E)-1-(2-methyl-1,3-thiazol-
    4-yl)prop-1-en-2-yl]-17-oxa-13-azabicyclo[14.1.0]
    heptadecane-8,12-dione
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.158.736
Chemical and physical data
FormulaC27H42N2O5S
Molar mass506.70 g·mol−1
3D model (JSmol)
SMILES
  • Cc3nc(/C=C(\C)[C@@H]1C[C@@H]2O[C@]2(C)CCC[C@H](C)[C@H](O)[C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)N1)cs3
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 Y
  • Key:FABUFPQFXZVHFB-PVYNADRNSA-N Y
 NY (what is this?)  (verify)

History

Ixabepilone is a semi-synthetic analog of epothilone B, a natural chemical compound produced by Sorangium cellulosum.[2] Epothilone B itself could not be developed as a pharmaceutical drug because of poor metabolic stability and pharmacokinetics.[3] Ixabepilone was designed through medicinal chemistry to improve upon these properties.[3]

Pharmacology

Much like Taxol, Ixabepilone acts to stabilize microtubules.[4][5][6] It is highly potent, capable of damaging cancer cells in very low concentrations, and retains activity in cases where tumor cells are insensitive to taxane type drugs.[7]

Approval

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.[8] In November 2008, the EMEA has refused a marketing authorisation for Ixabepilone.[9]

Ixabepilone is administered through injection, and is marketed under the trade name Ixempra.

Clinical uses

Ixabepilone, in combination with capecitabine, has demonstrated effectiveness in the treatment of metastatic or locally advanced breast cancer in patients after failure of an anthracycline and a taxane.[10]

It has been investigated for use in treatment of non-Hodgkin's lymphoma.[11] In pancreatic cancer phase two trial it showed some promising results (used alone). Combination therapy trials are ongoing.[7]

References
  1. "More information on cancer drugs". www.cancer.org.
  2. Goodin S (May 2008). "Novel cytotoxic agents: epothilones". Am J Health Syst Pharm. 65 (10 Suppl 3): S10–5. doi:10.2146/ajhp080089. PMID 18463327.
  3. Lee FY, Borzilleri R, Fairchild CR, et al. (December 2008). "Preclinical discovery of ixabepilone, a highly active antineoplastic agent". Cancer Chemother. Pharmacol. 63 (1): 157–66. doi:10.1007/s00280-008-0724-8. PMID 18347795.
  4. Lopus, M; Smiyun, G; Miller, H; Oroudjev, E; Wilson, L; Jordan, MA (2015). "Mechanism of action of ixabepilone and its interactions with the βIII-tubulin isotype". Cancer Chemother Pharmacol. 76 (5): 1013–24. doi:10.1007/s00280-015-2863-z. PMID 26416565. S2CID 1842156.
  5. Denduluri N, Swain SM (March 2008). "Ixabepilone for the treatment of solid tumors: a review of clinical data". Expert Opin Investig Drugs. 17 (3): 423–35. doi:10.1517/13543784.17.3.423. PMID 18321240. S2CID 71169099.
  6. Goodin S (November 2008). "Ixabepilone: a novel microtubule-stabilizing agent for the treatment of metastatic breast cancer". Am J Health Syst Pharm. 65 (21): 2017–26. doi:10.2146/ajhp070628. PMID 18945860.
  7. M. Vulfovich; Rocha-Lima, C; et al. (2008). "Novel advances in pancreatic cancer treatment". Expert Rev Anticancer Ther. 8 (6): 993–1002. doi:10.1586/14737140.8.6.993. PMID 18533808. S2CID 20049942.
  8. "FDA Approves IXEMPRA(TM) (ixabepilone), A Semi-Synthetic Analog Of Epothilone B, For The Treatment Of Advanced Breast Cancer". Medical News Today.
  9. London, 20 November 2008 Doc. Ref. EMEA/602569/2008
  10. Thomas ES, Gomez HL, Li RK, et al. (November 2007). "Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment". J. Clin. Oncol. 25 (33): 5210–7. doi:10.1200/JCO.2007.12.6557. PMID 17968020. Archived from the original on 2013-04-15.
  11. Aghajanian C, Burris HA, Jones S, et al. (March 2007). "Phase I study of the novel epothilone analog ixabepilone (BMS-247550) in patients with advanced solid tumors and lymphomas". J. Clin. Oncol. 25 (9): 1082–8. doi:10.1200/JCO.2006.08.7304. PMID 17261851. Archived from the original on 2013-04-15.
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