Azaepothilone B and its derivatives: a patent review

ABSTRACT

Introduction: Azaepothilone B, also known as ixabepilone, is a semi synthetic second generation epothilone B analogue. Azaepothilone B, its derivatives, and analogues, are used for treating advance metastatic breast cancer. It has been used as a chemotherapeutic medication for cancer.

Areas covered: This review highlights the patents on different routes for synthesis of azaepothilone B, its derivatives and analogues. The review will also provide the reported pharmacological activity and its polymorphs in the treatment of several cancers, such as breast cancer (metastatic or locally advanced), non-Hodgkin’s lymphoma, and pancreatic cancer. In addition, it considers other proliferative diseases such as viral infections, degenerative diseases of the musculoskeletal system, kidney disease, and immune response related diseases. Different databases such as Espacenet, ISI Web of Knowledge, Patbase, and Thomson Innovation have been searched extensively to review the patents. The analysis has been done to indicate the patenting trend across years and the comparison of active assignees.

Expert opinion: Azaepothilone B, along with its derivatives and analogues, can damage cancer cells in very low concentrations and retain its activity when tumor cells are insensitive to paclitaxel. Hence, it is highly potent agent. Azaepothilone B alone, in combination with other chemotherapeutics, or in the form of formulations, led to applications in various types of cancer. Also, antiproliferative activity of azaepothilone B has great potential for the treatment of proliferative diseases, such as skin diseases and infections. Recent progress in synthesizing azaepothilone B has encouraged researchers to develop new methods for the synthesis of azaepothilone B, its derivatives, and analogues, to obtain maximum yield in minimum steps.

KEYWORDS:

• Breast cancer
• microtubule-stabilizing agent
• azaepothilone B
• antiproliferative
• cytostatic
• epothilone B
• Sorangium cellulosum

Article highlights

• Patent literature on azaepothilone B, its derivatives and analogues with a focus on different synthesis processes and therapeutic uses is reviewed.

• Azaepothilone B has demonstrated effectiveness in the treatment of metastatic or locally advanced breast cancer in patients after failure of other chemotherapeutics.

• Azaepothilone B is administered through intravenous injection, and is marketed under the trade name Ixempra® by Bristol-Myers Squibb.

• Azaepothilone B is the potential agent for neurodegenerative disease associated with proliferative processes.

• Current research trend of synthesis and use of azaepothilone B, its derivatives and analogues is presented.

This box summarizes key points contained in the article.

Acknowledgments

We would like to thank Dr. R.R. Hirwani, Head, CSIR – Unit for Research and Development of Information Products (URDIP), Pune for giving us an opportunity to work on this project and providing necessary facilities in the research unit. We would also like to thank Ms .R. Jansi and Mr. Pradeep Biradar for providing the necessary technical support to write the review article.

Declaration of interest

The project was supported by the Council of Scientific and Industrial Research, India. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Supplementary material

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