WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 201610
Description: Ixabepilone (also known as azaepothilone B, or BMS-247550) is an orally bioavailable microtubule inhibitor. Ixabepilone was a semisynthetic analogue of epothilone B with antineoplastic activity. Ixabepilone binds to tubulin and promotes tubulin polymerization and microtubule stabilization, thereby arresting cells in the G2-M phase of the cell cycle and inducing tumor cell apoptosis. This agent demonstrates antineoplastic activity against taxane-resistant cell lines. Ixabepilone was approved in 2007. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus) (last updated: 7/10/2015).
MedKoo Cat#: 201610
Chemical Formula: C27H42N2O5S
Exact Mass: 506.28144
Molecular Weight: 506.7
Elemental Analysis: C, 64.00; H, 8.35; N, 5.53; O, 15.79; S, 6.33
Synonym: BMS247550; BMS-247550; BMS 247550; Azaepothilone BBMS 2475501. Trade name: Ixempra.
IUPAC/Chemical Name: (1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-((Z)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)-17-oxa-4-azabicyclo[14.1.0]heptadecane-5,9-dione
InChi Key: FABUFPQFXZVHFB-PVYNADRNSA-N
InChi Code: 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
SMILES Code: O=C(C[C@@H]1O)N[C@H](/C(C)=C/C2=CSC(C)=N2)C[C@H]3[C@@](O3)(C)CCC[C@H](C)[C@H](O)[C@@H](C)C(C1(C)C)=O
Ixabepilone (INN; also known as azaepothilone B, codenamed BMS-247550) is an epothilone B analog developed by Bristol-Myers Squibb as a cancer drug. It is produced by Sorangium cellulosum. 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.
IXEMPRA (ixabepilone) is a microtubule inhibitor belonging to a class of antineoplastic agents, the epothilones and their analogs. The epothilones are isolated from the myxobacterium Sorangium cellulosum. Ixabepilone is a semisynthetic analog of epothilone B, a 16-membered polyketide macrolide, with a chemically modified lactam substitution for the naturally existing lactone.
Ixabepilone is a semi-synthetic analog of epothilone B. Ixabepilone binds directly to β-tubulin subunits on microtubules, leading to suppression of microtubule dynamics. Ixabepilone suppresses the dynamic instability of αβ-II and αβ-III microtubules. Ixabepilone possesses low in vitro susceptibility to multiple tumor resistance mechanisms including efflux transporters, such as MRP-1 and P-glycoprotein (P-gp). Ixabepilone blocks cells in the mitotic phase of the cell division cycle, leading to cell death.
In cancer patients, ixabepilone has a plasma concentration-dependent effect on tubulin dynamics in peripheral blood mononuclear cells that is observed as the formation of microtubule bundles. Ixabepilone has antitumor activity in vivo against multiple human tumor xenografts, including drug-resistant types that overexpress P-gp, MRP-1, and βIII tubulin isoforms, or harbor tubulin mutations. Ixabepilone is active in xenografts that are resistant to multiple agents including taxanes, anthracyclines, and vinca alkaloids. Ixabepilone demonstrated synergistic antitumor activity in combination with capecitabine in vivo. In addition to direct antitumor activity, ixabepilone has antiangiogenic activity.
Chemical structure comparison between Ixabepilone (azaepothilone B or BMS-247550) and Patupilone (Epothilone B)
1: Smaglo BG, Pishvaian MJ. Profile and potential of ixabepilone in the treatment of pancreatic cancer. Drug Des Devel Ther. 2014 Jul 14;8:923-930. eCollection 2014. Review. PubMed PMID: 25075175; PubMed Central PMCID: PMC4106923.
2: Valero V. Managing ixabepilone adverse events with dose reduction. Clin Breast Cancer. 2013 Feb;13(1):1-6. doi: 10.1016/j.clbc.2012.09.003. Epub 2012 Oct 24. Review. PubMed PMID: 23098573.
3: Denduluri N, Swain S. Ixabepilone: clinical role in metastatic breast cancer. Clin Breast Cancer. 2011 Jun;11(3):139-45. doi: 10.1016/j.clbc.2011.03.009. Epub 2011 Apr 20. Review. PubMed PMID: 21665133.
4: Alvarez RH, Valero V, Hortobagyi GN. Ixabepilone for the treatment of breast cancer. Ann Med. 2011;43(6):477-86. doi: 10.3109/07853890.2011.579151. Epub 2011 May 17. Review. PubMed PMID: 21585248.
5: Kaklamani VG, Xu BH, Gomez HL. Global experience with ixabepilone in breast cancer. Expert Rev Anticancer Ther. 2011 May;11(5):683-92. doi: 10.1586/era.11.41. Review. PubMed PMID: 21554041.
6: Rivera E, Gomez H. Chemotherapy resistance in metastatic breast cancer: the evolving role of ixabepilone. Breast Cancer Res. 2010;12 Suppl 2:S2. doi: 10.1186/bcr2573. Epub 2010 Oct 22. Review. PubMed PMID: 21050423; PubMed Central PMCID: PMC2972556.
7: Fornier M. Ixabepilone plus capecitabine for breast cancer patients with an early metastatic relapse after adjuvant chemotherapy: two clinical trials. Clin Breast Cancer. 2010 Oct 1;10(5):352-8. doi: 10.3816/CBC.2010.n.046. Review. PubMed PMID: 20920979.
8: Egerton N. Optimizing ixabepilone treatment schedules in patients with advanced or metastatic breast cancer. Cancer Chemother Pharmacol. 2010 Nov;66(6):1005-12. doi: 10.1007/s00280-010-1467-x. Epub 2010 Oct 1. Review. PubMed PMID: 20886213; PubMed Central PMCID: PMC2955910.
9: Perez EA, Patel T, Moreno-Aspitia A. Efficacy of ixabepilone in ER/PR/HER2-negative (triple-negative) breast cancer. Breast Cancer Res Treat. 2010 Jun;121(2):261-71. doi: 10.1007/s10549-010-0824-0. Epub 2010 Mar 13. Review. PubMed PMID: 20229176.
10: Kossoff E. Alternative dosing schedules and administration updates for ixabepilone. J Oncol Pharm Pract. 2011 Sep;17(3):203-8. doi: 10.1177/1078155210364273. Epub 2010 Mar 9. Review. PubMed PMID: 20215481.
11: Li L, Li J, Yang K, Tian J, Sun T, Jia W, Zhang P, Yi K. Ixabepilone plus capecitabine with capecitabine alone for metastatic breast cancer. Future Oncol. 2010 Feb;6(2):201-7. doi: 10.2217/fon.09.162. Review. PubMed PMID: 20146579.
12: Yardley DA. Visceral disease in patients with metastatic breast cancer: efficacy and safety of treatment with ixabepilone and other chemotherapeutic agents. Clin Breast Cancer. 2010 Feb;10(1):64-73. doi: 10.3816/CBC.2010.n.009. Review. PubMed PMID: 20133261.
13: Stein A. Ixabepilone. Clin J Oncol Nurs. 2010 Feb;14(1):65-71. doi: 10.1188/10.CJON.65-71. Review. PubMed PMID: 20118028.
14: Bourdeanu L, Wong SF. Supporting Asian patients with metastatic breast cancer during ixabepilone therapy. Expert Opin Drug Saf. 2010 May;9(3):383-96. doi: 10.1517/14740331003592082. Review. PubMed PMID: 20105113.
15: Harichand-Herdt S, O'regan RM. Identifying subsets of metastatic breast cancer patients likely to benefit from treatment with the epothilone B analog ixabepilone. Am J Clin Oncol. 2010 Dec;33(6):561-7. doi: 10.1097/COC.0b013e3181c4c6ae. Review. PubMed PMID: 20051810.
16: Bertino EM, Ramaswamy B. Ixabepilone as monotherapy or in combination for the treatment of advanced breast cancer. Breast Cancer (Dove Med Press). 2010 May 24;2:13-23. Review. PubMed PMID: 24367163; PubMed Central PMCID: PMC3846877.
17: Toppmeyer DL, Goodin S. Ixabepilone, a new treatment option for metastatic breast cancer. Am J Clin Oncol. 2010 Oct;33(5):516-21. doi: 10.1097/COC.0b013e3181b9cd52. Review. PubMed PMID: 20023567.
18: Frye DK. Advances in breast cancer treatment: the emerging role of ixabepilone. Expert Rev Anticancer Ther. 2010 Jan;10(1):23-32. doi: 10.1586/era.09.158. Review. PubMed PMID: 20014882.
19: Moen MD. Ixabepilone: in locally advanced or metastatic breast cancer. Drugs. 2009 Jul 30;69(11):1471-81. doi: 10.2165/00003495-200969110-00006. Review. PubMed PMID: 19634925.
20: Yardley DA. Proactive management of adverse events maintains the clinical benefit of ixabepilone. Oncologist. 2009 May;14(5):448-55. doi: 10.1634/theoncologist.2008-0284. Epub 2009 May 1. Review. PubMed PMID: 19411315.