Ixabepilone
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MedKoo CAT#: 201610

CAS#: 219989-84-1

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).


Chemical Structure

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Ixabepilone
CAS# 219989-84-1

Theoretical Analysis

MedKoo Cat#: 201610
Name: Ixabepilone
CAS#: 219989-84-1
Chemical Formula: C27H42N2O5S
Exact Mass: 506.2814
Molecular Weight: 506.702
Elemental Analysis: C, 64.00; H, 8.35; N, 5.53; O, 15.79; S, 6.33

Price and Availability

Size Price Availability Quantity
25.0mg USD 2950.0 2 Weeks
50.0mg USD 3950.0 2 Weeks
100.0mg USD 5950.0 2 Weeks
200.0mg USD 8950.0 2 Weeks
500.0mg USD 14950.0 2 Weeks
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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

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Ixabepilone (BMS-247550) is an orally bioavailable microtubule inhibitor, which binds to tubulin and promotes tubulin polymerization and microtubule stabilization, thereby arrests cells in the G2-M phase of the cell cycle and induces tumor cell apoptosis.
In vitro activity: Ixabepilone effectively decreased the viability of parental 231C cells in a concentration-dependent manner (Fig. 1A). Ixabepilone was also active in docetaxel-resistant TXT cells, although not to the same extent as in 231C cells (Fig. 1A). Reference: Pharmacol Rep. 2022 Oct;74(5):998-1010. https://pubmed.ncbi.nlm.nih.gov/35908023/
In vivo activity: The antitumor efficacy of ixabepilone in combination with bevacizumab, an anti-angiogenic monoclonal antibody that inhibits vascular endothelial growth factor (VEGF), was evaluated in L2987 human lung carcinoma xenografts grown in nude mice [Lee et al. 2008b]. Administration of ixabepilone in combination with bevacizumab produced significantly greater antitumor activity than single-agent ixabepilone alone at its MTD (p = 0.003) or bevacizumab alone at its MTD (p = 0.0008). Reference: Ther Adv Med Oncol. 2011 Jan;3(1):11-25. https://pubmed.ncbi.nlm.nih.gov/21789152/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 20.0 39.47
DMSO 49.44 97.58
Ethanol 33.5 66.11
Ethanol:PBS (pH 7.2) (1:1) 0.5 0.99

Preparing Stock Solutions

The following data is based on the product molecular weight 506.702 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Tam S, Al-Zubaidi Y, Rahman MK, Bourget K, Zhou F, Murray M. The ixabepilone and vandetanib combination shows synergistic activity in docetaxel-resistant MDA-MB-231 breast cancer cells. Pharmacol Rep. 2022 Oct;74(5):998-1010. doi: 10.1007/s43440-022-00396-7. Epub 2022 Jul 30. PMID: 35908023; PMCID: PMC9584993. 2. Tanei T, Choi DS, Rodriguez AA, Liang DH, Dobrolecki L, Ghosh M, Landis MD, Chang JC. Antitumor activity of Cetuximab in combination with Ixabepilone on triple negative breast cancer stem cells. Breast Cancer Res. 2016 Jan 12;18(1):6. doi: 10.1186/s13058-015-0662-4. PMID: 26757880; PMCID: PMC4711100. 3. Lee F, Jure-Kunkel MN, Salvati ME. Synergistic activity of ixabepilone plus other anticancer agents: preclinical and clinical evidence. Ther Adv Med Oncol. 2011 Jan;3(1):11-25. doi: 10.1177/1758834010386402. PMID: 21789152; PMCID: PMC3126033.
In vitro protocol: 1. Tam S, Al-Zubaidi Y, Rahman MK, Bourget K, Zhou F, Murray M. The ixabepilone and vandetanib combination shows synergistic activity in docetaxel-resistant MDA-MB-231 breast cancer cells. Pharmacol Rep. 2022 Oct;74(5):998-1010. doi: 10.1007/s43440-022-00396-7. Epub 2022 Jul 30. PMID: 35908023; PMCID: PMC9584993. 2. Tanei T, Choi DS, Rodriguez AA, Liang DH, Dobrolecki L, Ghosh M, Landis MD, Chang JC. Antitumor activity of Cetuximab in combination with Ixabepilone on triple negative breast cancer stem cells. Breast Cancer Res. 2016 Jan 12;18(1):6. doi: 10.1186/s13058-015-0662-4. PMID: 26757880; PMCID: PMC4711100.
In vivo protocol: 1. Lee F, Jure-Kunkel MN, Salvati ME. Synergistic activity of ixabepilone plus other anticancer agents: preclinical and clinical evidence. Ther Adv Med Oncol. 2011 Jan;3(1):11-25. doi: 10.1177/1758834010386402. PMID: 21789152; PMCID: PMC3126033.

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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.



Additional Information

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)