Ixabepilone (
INN
Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...
; also known as azaepothilone B, codenamed BMS-247550) is a pharmaceutical drug developed by
Bristol-Myers Squibb
The Bristol Myers Squibb Company (BMS) is an American multinational pharmaceutical company. Headquartered in New York City, BMS is one of the world's largest pharmaceutical companies and consistently ranks on the ''Fortune'' 500 list of the lar ...
as a
chemotherapeutic
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
medication for cancer.
History
Ixabepilone is a
semi-synthetic
Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis that uses chemical compounds isolated from natural sources (such as microbial cell cultures or plant material) as the starting materials to produce novel compounds with ...
analog
Analog or analogue may refer to:
Computing and electronics
* Analog signal, in which information is encoded in a continuous variable
** Analog device, an apparatus that operates on analog signals
*** Analog electronics, circuits which use analog ...
of
epothilone
Epothilones are a class of potential cancer drugs. Like taxanes, they prevent cancer cells from dividing by interfering with tubulin, but in early trials, epothilones have better efficacy and milder adverse effects than taxanes.
, epothilones A t ...
B, a natural chemical compound produced by ''
Sorangium cellulosum
''Sorangium cellulosum'' is a soil-dwelling Gram-negative bacterium of the group myxobacteria. It is motile and shows gliding motility. Under stressful conditions this motility, as in other myxobacteria, the cells congregate to form fruiting bodi ...
''.
Epothilone B itself could not be developed as a pharmaceutical drug because of poor
metabolic stability
Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set o ...
and
pharmacokinetics
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...
.
Ixabepilone was designed through
medicinal chemistry
Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with designing and developing pharmaceutical drugs. Medicinal chemistry involves the identification, synthesis and developm ...
to improve upon these properties.
Pharmacology
Much like
Taxol
Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cance ...
, Ixabepilone acts to stabilize
microtubule
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...
s.
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
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
approved ixabepilone for the treatment of aggressive
metastatic
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
or locally advanced
breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...
no longer responding to currently available chemotherapies. In November 2008, the
EMEA
EMEA is a shorthand designation meaning Europe, the Middle East and Africa. The acronym is used by institutions and governments, as well as in marketing and business when referring to this region: it is a shorthand way of referencing the two ...
has refused a marketing authorisation for Ixabepilone.
[London, 20 November 2008 Doc. Ref. EMEA/602569/2008]
Ixabepilone is administered through injection, and is marketed under the trade name Ixempra.
Clinical uses
Ixabepilone, in combination with
capecitabine
Capecitabine, sold under the brand name Xeloda among others, is a chemotherapy medication used to treat breast cancer, gastric cancer and colorectal cancer. For breast cancer it is often used together with docetaxel. It is taken by mouth.
Comm ...
, has demonstrated effectiveness in the treatment of metastatic or locally advanced breast cancer in patients after failure of an
anthracycline
Anthracyclines are a class of drugs used in cancer chemotherapy that are extracted from ''Streptomyces'' bacterium. These compounds are used to treat many cancers, including leukemias, lymphomas, breast, stomach, uterine, ovarian, bladder cance ...
and a
taxane
Taxanes are a class of diterpenes. They were originally identified from plants of the genus ''Taxus'' (yews), and feature a taxadiene core. Paclitaxel (Taxol) and docetaxel (Taxotere) are widely used as chemotherapy agents. Cabazitaxel was FDA ap ...
.
It has been investigated for use in treatment of
non-Hodgkin's lymphoma
Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include lymphadenopathy, enlarged lymph nodes, fever, night sweats, weight los ...
.
In pancreatic cancer phase two trial it showed some promising results (used alone). Combination therapy trials are ongoing.
References
External links
Ixempra product websiteIxempra prescribing information
{{Chemotherapeutic agents
Bristol Myers Squibb
Mitotic inhibitors
Thiazoles
Epoxides
Lactams