Ixabepilone

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Cat Number

API0232144

CAS Number

219989-84-1

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Product Detail Description Scientific Support Customer Q&A

CAS Number

219989-84-1

EINECS

630-424-7

Storage

Store at 2-8°C

Synonyms

Azaepothilone B; Ixempra; BMS-247550; ixabepilona; NSC-747973

Molecular Formula

C27H42N2O5S

Molecular Weight

506.7

Smiles

C[C@H]1CCC[C@@]2([C@@H](O2)C[C@H](NC(=O)C[C@@H](C(C(=O)[C@@H]([C@H]1O)C)(C)C)O)/C(=C/C3=CSC(=N3)C)/C)C

Melting Point

>160°C (dec.)

Boiling Point

697.8±55.0°C at 760 mmHg (Predicted)

Relative Density

1.122±0.06 (Predicted)

General Description

Ixabepilone is a semisynthetic analogue of epothilone B, a natural macrolide antibiotic isolated from the myxobacterium Sorangium cellulosum. Its chemical structure is a lactam analog of epothilone B, containing a 16‑membered macrolactone ring with a thiazole side chain. Ixabepilone is a microtubule‑stabilizing agent that binds to tubulin at a site distinct from the taxanes.

Mechanism of Action

Ixabepilone binds to β‑tubulin on the taxane binding site but with higher affinity and different conformational effects than paclitaxel. It promotes tubulin polymerization into stable microtubules and prevents their depolymerization, leading to mitotic arrest and apoptosis. Unlike taxanes, ixabepilone is not a substrate for P‑glycoprotein (P‑gp) and retains activity against multidrug‑resistant (MDR) tumors.

Application

Ixabepilone is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer that has progressed after anthracycline and taxane therapy. It is also indicated in combination with capecitabine for taxane‑resistant breast cancer. The drug is effective against tumors that overexpress P‑gp, providing a treatment option for patients resistant to paclitaxel or docetaxel.

Ten breast cancer patients receiving ixabepilone underwent neuropathy assessments and skin biopsies at cumulative doses of 80‑90, 160‑190, and >200 mg/m². Total Neuropathy Score increased dose‑dependently. Electron microscopy showed progressive axonal loss (increased empty Schwann cells, dilated axons) and mitochondrial abnormalities: axon profiles without mitochondria increased from 71% at baseline to 78% by cycle 7, and mitochondria with severe abnormal morphology rose from 24% to 79%. Perineuronal macrophage infiltration was noted. Ixabepilone causes dose‑dependent small fiber neuropathy with cumulative mitochondrial toxicity, detectable by serial skin biopsy.

Fig. 1 Effect of Ixabepilone on axonal mitochondria of Remak Schwann cells. (Ebenezer GJ, et al., 2014)

References

Ebenezer GJ, et al. Ixabepilone-induced mitochondria and sensory axon loss in breast cancer patients. Ann Clin Transl Neurol. 2014;1(9):639-649.

Does Ixabepilone require refrigerated storage as an epothilone analog?

Yes, it must be stored at 2-8°C. The lactone ring is thermally labile; at room temperature, rapid ring-opening and isomerization occur.

Is Ixabepilone sensitive to light and moisture during handling?

Yes, it is photosensitive and hygroscopic. Store in light-resistant, moisture-proof containers under refrigeration. Handle under subdued light.

What is the stability of Ixabepilone after reconstitution for intravenous infusion?

Reconstituted solutions (in D5W or saline) are stable for up to 24 hours under refrigeration.

How is the impurity ixabepilone ring-opened derivative (a hydrolysis product) monitored?

This primary degradation product is specifically quantified using a stability-indicating HPLC method, ensuring it remains within ICH limits.