A patent review of adaptor associated kinase 1 (AAK1) inhibitors (2013-present)

ABSTRACT

Introduction

Adaptor-associated kinase 1 (AAK1) has been proposed as being a promising drug target for the treatment of a variety of neurological and psychiatric disorders, such as schizophrenia, cognitive deficits in schizophrenia, Parkinson’s disease, bipolar disorder, Alzheimer’s disease and neuropathic pain. More recently, AAK1 was shown to be an essential cellular factor for viral replication and therefore has been pursued as a host target for the development of broad-spectrum antiviral agents.

Areas covered

This review provides an overview of the patented AAK1 inhibitors from 2013 to present.

Expert opinion

The promise of AAK1 as drug target for the treatment of neuropathic pain stimulated the search for AAK1 inhibitors. However, only two companies (i.e. Lexicon Pharmaceuticals and Bristol Myers Squibb) seemed to be active in this field and filed patent applications in the last few years. The most promising congeners showed promising in vitro activity in a variety of AAK1-related assays. Moreover, selected compounds were also endowed with in vivo activity in various preclinical animal models for neuropathic pain.

KEYWORDS:

• Adaptor-associated kinase 1
• antiviral agents
• neurological disorders
• neuropathic pain

Article highlights

• AAK1 is a promising drug target for the treatment of neuropathic pain.

• More recently, AAK1 is being pursued for the development of broad spectrum antiviral agents.

• Two pharmaceutical companies (Lexicon Pharmaceuticals and Bristol Myers Squibb) are active in the synthesis of AAK1 inhibitors.

• Potent, selective and drug-like AAK1 inhibitors, based on various chemotypes, are available.

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.