Ixabepilone
Clinical data | |
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Trade names | Ixempra |
Other names | Azaepothilone B |
AHFS/Drugs.com | Monograph |
MedlinePlus | a608042 |
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Routes of administration | Intravenous infusion |
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Pharmacokinetic data | |
Bioavailability | N/A |
Protein binding | 67 to 77% |
Metabolism | Extensive, hepatic, CYP3A4-mediated |
Elimination half-life | 52 hours |
Excretion | Fecal (mostly) and renal |
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ECHA InfoCard | 100.158.736 |
Chemical and physical data | |
Formula | C27H42N2O5S |
Molar mass | 506.70 g·mol−1 |
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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]
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[]
- ^ "More information on cancer drugs". www.cancer.org.
- ^ 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.
- ^ a b 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ a b 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.
- ^ "FDA Approves IXEMPRA(TM) (ixabepilone), A Semi-Synthetic Analog Of Epothilone B, For The Treatment Of Advanced Breast Cancer". Medical News Today.
- ^ London, 20 November 2008 Doc. Ref. EMEA/602569/2008
- ^ 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.
- ^ 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.
External links[]
- Bristol-Myers Squibb
- Mitotic inhibitors
- Thiazoles
- Epoxides
- Lactams