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.^[2]

Ixabepilone

Clinical data
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: WARNING[1]Rx-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.^[3] 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.^[4] Ixabepilone was designed through medicinal chemistry to improve upon these properties.^[4]

Pharmacology

Much like Taxol, Ixabepilone acts to stabilize microtubules.^[5][6][7] 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.^[8]

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.^[9] In November 2008, the EMEA has refused a marketing authorisation for Ixabepilone.^[10]

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.^[11]

It has been investigated for use in treatment of non-Hodgkin's lymphoma.^[12] In pancreatic cancer phase two trial it showed some promising results (used alone). Combination therapy trials are ongoing.^[8]

References

1. "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
2. "More information on cancer drugs". www.cancer.org.
3. Goodin S (May 2008). "Novel cytotoxic agents: epothilones". American Journal of Health-System Pharmacy. 65 (10 Suppl 3): S10–S15. doi:10.2146/ajhp080089. PMID 18463327.
4. Lee FY, Borzilleri R, Fairchild CR, Kamath A, Smykla R, Kramer R, Vite G (December 2008). "Preclinical discovery of ixabepilone, a highly active antineoplastic agent". Cancer Chemotherapy and Pharmacology. 63 (1): 157–166. doi:10.1007/s00280-008-0724-8. PMID 18347795.
5. Lopus M, Smiyun G, Miller H, Oroudjev E, Wilson L, Jordan MA (November 2015). "Mechanism of action of ixabepilone and its interactions with the βIII-tubulin isotype". Cancer Chemotherapy and Pharmacology. 76 (5): 1013–1024. doi:10.1007/s00280-015-2863-z. PMID 26416565. S2CID 1842156.
6. Denduluri N, Swain SM (March 2008). "Ixabepilone for the treatment of solid tumors: a review of clinical data". Expert Opinion on Investigational Drugs. 17 (3): 423–435. doi:10.1517/13543784.17.3.423. PMID 18321240. S2CID 71169099.
7. Goodin S (November 2008). "Ixabepilone: a novel microtubule-stabilizing agent for the treatment of metastatic breast cancer". American Journal of Health-System Pharmacy. 65 (21): 2017–2026. doi:10.2146/ajhp070628. PMID 18945860.
8. Vulfovich M, Rocha-Lima C (June 2008). "Novel advances in pancreatic cancer treatment". Expert Review of Anticancer Therapy. 8 (6): 993–1002. doi:10.1586/14737140.8.6.993. PMID 18533808. S2CID 20049942.
9. "FDA Approves IXEMPRA(TM) (ixabepilone), A Semi-Synthetic Analog Of Epothilone B, For The Treatment Of Advanced Breast Cancer". Medical News Today.
10. "Questions and answers on recommendation for the refusal of the marketing authorisation for Ixempra" (PDF). European Medicines Agency. London. 20 November 2008. Doc. Ref. EMEA/602569/2008.
11. Thomas ES, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, et al. (November 2007). "Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment". Journal of Clinical Oncology. 25 (33): 5210–5217. doi:10.1200/JCO.2007.12.6557. PMID 17968020.
12. Aghajanian C, Burris HA, Jones S, Spriggs DR, Cohen MB, Peck R, et al. (March 2007). "Phase I study of the novel epothilone analog ixabepilone (BMS-247550) in patients with advanced solid tumors and lymphomas". Journal of Clinical Oncology. 25 (9): 1082–1088. doi:10.1200/JCO.2006.08.7304. PMID 17261851.

External links

• Ixempra product website
• Ixempra prescribing information