Ixabepilone

History

Ixabepilone is a semi-synthetic analog of epothilone B, a natural chemical compound produced by Sorangium cellulosum. The structural difference between Epothilone B and Ixabepilone consists of only a single atom oxygen-to-nitrogen subsitution that converts the ester into an amide. Epothilone B itself could not be developed as a pharmaceutical drug because of poor metabolic stability and pharmacokinetics. Ixabepilone was designed through medicinal chemistry to improve upon these properties.

Pharmacology

Much like Taxol, Ixabepilone acts to stabilize microtubules. 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.

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. In November 2008, the EMEA has refused a marketing authorisation for Ixabepilone.

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.

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

References

References

1. "More information on cancer drugs".
2. (May 2008). "Novel cytotoxic agents: epothilones". American Journal of Health-System Pharmacy.
3. (December 2008). "Preclinical discovery of ixabepilone, a highly active antineoplastic agent". Cancer Chemotherapy and Pharmacology.
4. (November 2015). "Mechanism of action of ixabepilone and its interactions with the βIII-tubulin isotype". Cancer Chemotherapy and Pharmacology.
5. (March 2008). "Ixabepilone for the treatment of solid tumors: a review of clinical data". Expert Opinion on Investigational Drugs.
6. (November 2008). "Ixabepilone: a novel microtubule-stabilizing agent for the treatment of metastatic breast cancer". American Journal of Health-System Pharmacy.
7. (June 2008). "Novel advances in pancreatic cancer treatment". Expert Review of Anticancer Therapy.
8. "FDA Approves IXEMPRA(TM) (ixabepilone), A Semi-Synthetic Analog Of Epothilone B, For The Treatment Of Advanced Breast Cancer".
9. (20 November 2008). "Questions and answers on recommendation for the refusal of the marketing authorisation for Ixempra". European Medicines Agency.
10. (November 2007). "Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment". Journal of Clinical Oncology.
11. (March 2007). "Phase I study of the novel epothilone analog ixabepilone (BMS-247550) in patients with advanced solid tumors and lymphomas". Journal of Clinical Oncology.