Ixabepilone

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Ixabepilone
Ixabepilone.svg
Systematic (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
Clinical data
Trade names Ixempra
AHFS/Drugs.com monograph
MedlinePlus a608042
Licence data US FDA:link
Pregnancy cat. D (US)
Legal status -only (US)
Routes Intravenous infusion
Pharmacokinetic data
Bioavailability N/A
Protein binding 67 to 77%
Metabolism Extensive, hepatic, CYP3A4-mediated
Half-life 52 hours
Excretion Fecal (mostly) and renal
Identifiers
CAS number 219989-84-1 N
ATC code L01DC04
PubChem CID 6445540
DrugBank DB04845
ChemSpider 20145579 YesY
UNII K27005NP0A YesY
KEGG D04645 YesY
ChEMBL CHEMBL1201752 N
Synonyms Azaepothilone B
Chemical data
Formula C27H42N2O5S 
Mol. mass 506.698 g/mol
 N (what is this?)  (verify)

Ixabepilone (INN; also known as azaepothilone B, codenamed BMS-247550) is an epothilone B analog[1] developed by Bristol-Myers Squibb as a chemotherapeutic medication for cancer.[2]

It is produced by Sorangium cellulosum.[3]

Pharmacology[edit]

It acts to stabilize microtubules.[4][5] It is highly potent agent, capable of damaging cancer cells in very low concentrations, and retains activity in cases where tumor cells are insensitive to paclitaxel.[6]

Approval[edit]

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.[7] In November 2008, the EMEA has refused a marketing authorisation for Ixabepilone.[8]

Ixabepilone is administered through injection, and is marketed under the trade name Ixempra.

Clinical uses[edit]

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.[9]

It has been investigated for use in treatment of non-Hodgkin's lymphoma.[10] In pancreatic cancer phase two trial it showed some promising results (used alone). Combination therapy trials are ongoing.[6]

References[edit]

  1. ^ 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. 
  2. ^ http://www.cancer.org/Treatment/TreatmentsandSideEffects/GuidetoCancerDrugs/Ixabepilone
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ a b M. Vulfovich et al; Rocha-Lima, C (2008). "Novel advances in pancreatic cancer treatment". Expert Rev Anticancer Ther 8 (6): 993–1002. doi:10.1586/14737140.8.6.993. PMID 18533808. 
  7. ^ Medical News Today
  8. ^ London, 20 November 2008 Doc. Ref. EMEA/602569/2008
  9. ^ 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. 
  10. ^ 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. 

External links[edit]