Ixabepilone

Ixabepilone
Names
Trade namesIxempra
Other namesAzaepothilone B,[1] BMS-247550
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
Clinical data
Drug classEpothilone, microtubule inhibitor[2]
Main usesBreast cancer[2]
Side effectsPeripheral neuropathy, tiredness, muscle pain, hair loss, nausea, inflammation of the mouth, diarrhea, low blood cells[3]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • US: D (Evidence of risk)
    Routes of
    use    		Intravenous infusion
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa608042
    Legal
    License data
    Legal status
    Pharmacokinetics
    BioavailabilityN/A
    Protein binding67 to 77%
    MetabolismExtensive, hepatic, CYP3A4-mediated
    Elimination half-life52 hours
    ExcretionFecal (mostly) and renal
    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 checkY
    • Key:FABUFPQFXZVHFB-PVYNADRNSA-N checkY

    Ixabepilone, also known as azaepothilone B, is a medication used to treat breast cancer.[2][1] It is used in people who fail other treatments.[2] It is used by gradual injection into a vein.[2]

    Common side effects include peripheral neuropathy, tiredness, muscle pain, hair loss, nausea, inflammation of the mouth, diarrhea, and low blood cells.[3] Other side effects may include allergic reactions, heart attack, and arrhythmia.[3][2] Use in pregnancy many harm the baby.[3] It is an epothilone and microtubule inhibitor.[2]

    Ixabepilone was approved for medical use in the United States in 2007.[2] In the United states it costs about 5,200 USD per 45 mg vial as of 2021.[4] It is sold under the brand name Ixempra.[3]

    Medical use

    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.[5]

    It has been investigated for use in treatment of non-Hodgkin's lymphoma.[6] In pancreatic cancer phase two trial it showed some promising results (used alone). Combination therapy trials are ongoing.[7]

    Dosage

    It is given at a dose of 40 mg/m2 body surface area every 21 days.[2]

    Pharmacology

    Much like Taxol, Ixabepilone acts to stabilize microtubules.[8][9][10] 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]

    History

    Ixabepilone is a semi-synthetic analog of epothilone B, a natural chemical compound produced by Sorangium cellulosum.[11] Epothilone B itself could not be developed as a pharmaceutical drug because of poor metabolic stability and pharmacokinetics.[12] Ixabepilone was designed through medicinal chemistry to improve upon these properties.[12]

    Society and culture

    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.[13] In November 2008, the EMEA has refused a marketing authorisation for Ixabepilone.[14]

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

    References

    1. 1 2 Mandhare, A; Biradar, S; Gurule, A (August 2016). "Azaepothilone B and its derivatives: a patent review". Expert opinion on therapeutic patents. 26 (8): 891–905. doi:10.1080/13543776.2016.1199688. PMID 27282355.
    2. 1 2 3 4 5 6 7 8 9 "Ixabepilone Monograph for Professionals". Drugs.com. Archived from the original on 25 July 2021. Retrieved 26 November 2021.
    3. 1 2 3 4 5 "DailyMed - IXEMPRA- ixabepilone kit". dailymed.nlm.nih.gov. Archived from the original on 22 April 2021. Retrieved 1 December 2021.
    4. ↑ "Ixempra Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 21 January 2021. Retrieved 1 December 2021.
    5. ↑ 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.
    6. ↑ 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.
    7. 1 2 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. ↑ 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.
    9. ↑ 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.
    10. ↑ 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.
    11. ↑ 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.
    12. 1 2 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.
    13. ↑ "FDA Approves IXEMPRA(TM) (ixabepilone), A Semi-Synthetic Analog Of Epothilone B, For The Treatment Of Advanced Breast Cancer". Medical News Today. Archived from the original on 2019-06-05. Retrieved 2021-02-07.
    14. ↑ London, 20 November 2008 Doc. Ref. EMEA/602569/2008
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