Chemistry:Ixabepilone
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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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| 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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| 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". https://www.cancer.org/treatment/treatments-and-side-effects/cancer-drugs.html.
- ↑ "Novel cytotoxic agents: epothilones". American Journal of Health-System Pharmacy 65 (10 Suppl 3): S10–S15. May 2008. doi:10.2146/ajhp080089. PMID 18463327.
- ↑ 3.0 3.1 "Preclinical discovery of ixabepilone, a highly active antineoplastic agent". Cancer Chemotherapy and Pharmacology 63 (1): 157–166. December 2008. doi:10.1007/s00280-008-0724-8. PMID 18347795.
- ↑ "Mechanism of action of ixabepilone and its interactions with the βIII-tubulin isotype". Cancer Chemotherapy and Pharmacology 76 (5): 1013–1024. November 2015. doi:10.1007/s00280-015-2863-z. PMID 26416565.
- ↑ "Ixabepilone for the treatment of solid tumors: a review of clinical data". Expert Opinion on Investigational Drugs 17 (3): 423–435. March 2008. doi:10.1517/13543784.17.3.423. PMID 18321240.
- ↑ "Ixabepilone: a novel microtubule-stabilizing agent for the treatment of metastatic breast cancer". American Journal of Health-System Pharmacy 65 (21): 2017–2026. November 2008. doi:10.2146/ajhp070628. PMID 18945860.
- ↑ 7.0 7.1 "Novel advances in pancreatic cancer treatment". Expert Review of Anticancer Therapy 8 (6): 993–1002. June 2008. doi:10.1586/14737140.8.6.993. PMID 18533808.
- ↑ "FDA Approves IXEMPRA(TM) (ixabepilone), A Semi-Synthetic Analog Of Epothilone B, For The Treatment Of Advanced Breast Cancer". https://www.medicalnewstoday.com/releases/85726.php.
- ↑ "Questions and answers on recommendation for the refusal of the marketing authorisation for Ixempra". European Medicines Agency. London. 20 November 2008. http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_Initial_authorisation/human/000930/WC500014746.pdf.
- ↑ "Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment". Journal of Clinical Oncology 25 (33): 5210–5217. November 2007. doi:10.1200/JCO.2007.12.6557. PMID 17968020.
- ↑ "Phase I study of the novel epothilone analog ixabepilone (BMS-247550) in patients with advanced solid tumors and lymphomas". Journal of Clinical Oncology 25 (9): 1082–1088. March 2007. doi:10.1200/JCO.2006.08.7304. PMID 17261851.
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