Ixabepilone

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]

Ixabepilone

Clinical data
Pronunciation	/ˌɪksəˈbɛpɪloʊn/ IKS-ə-BE-pi-lohn
Trade names	Ixempra
Other names	Azaepothilone B
AHFS/Drugs.com	Monograph
MedlinePlus	a608042
License data	US DailyMed: Ixabepilone US FDA: Ixabepilone
Routes of administration	Intravenous infusion
ATC code	L01DC04 (WHO)
Legal status
Legal status	US: ℞-only
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
Identifiers
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
CAS Number	219989-84-1 N
PubChem CID	6445540
IUPHAR/BPS	6824
DrugBank	DB04845 Y
ChemSpider	20145579 Y
UNII	K27005NP0A
KEGG	D04645 Y
ChEMBL	ChEMBL1201752 N
CompTox Dashboard (EPA)	DTXSID70870252
ECHA InfoCard	100.158.736
Chemical and physical data
Formula	C27H42N2O5S
Molar mass	506.70 g·mol−1
3D model (JSmol)	Interactive image
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 Y Key:FABUFPQFXZVHFB-PVYNADRNSA-N Y
NY (what is this?)  (verify)

History

Ixabepilone is a semi-synthetic analog of epothilone B, a natural chemical compound produced by Sorangium cellulosum.^[2] 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.^[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]