Inhibitors of the bone morphogenetic protein (BMP) signaling pathway: a patent review (2008-2015)

ABSTRACT

Introduction: The bone morphogenetic protein (BMP) is a critical signaling pathway and plays a diverse role in embryonic pattern formation and is implicated in a variety of disease processes, including anemia, bone formation, atherosclerosis, skin diseases, and cancers, among others.

Areas covered: This review covers small molecule inhibitors/antagonists of BMP in patent applications between 2008 – 2015, along with brief synopses of the disclosed inhibitors in the primary literature.

Expert opinion: The development of potent and selective BMP inhibitors is ongoing with most of the work centered around improving the selectivity and pharmacokinetic profile. Early work was for the treatment of the rare and neglected disease, fibrodysplasia ossificans progressiva (FOP). Recently, however, there has been increased interest in their use in a number of other diseases such as cancer, atherosclerosis, and anemia of chronic disease, to name a few. Although the primary participants in the early work were from academic laboratories, recently a significant surge from the pharmaceutical industry has elevated the interest in the development of BMP inhibitors for a wide-range of therapeutic indications. Due to this, expect a number of new approaches such as repurposing of other kinase inhibitors to be brought into clinical trials in the near future.

KEYWORDS:

• Bone morphogenetic protein
• BMP
• ALK
• inhibitors
• small molecule
• activin receptor-like kinase

Article highlights

• BMP inhibitors are being evaluated pre-clinically for a number of potential therapeutic indications, including fibrodysplasia ossificans progressiva (FOP), cancer, anemia, anemia of chronic disease, and atherosclerosis to name a few.

• The highest patent activity pertains to the pyrazolo[1,5-a]pyrimidine scaffold which is present in the originally disclosed inhibitor, dorsomorphin.

• New patents from both Harvard and Vanderbilt, however, disclose novel and selective BMP inhibitors.

• With the numerous areas of impact for BMP inhibitors, the number of disclosed inhibitors will more than certainly proliferate in the near future.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The author was supported by La Jolla Pharmaceuticals and Vanderbilt.