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

Expert Opin Ther Pat. 2021 Oct;31(10):911-936. doi: 10.1080/13543776.2021.1928637. Epub 2021 May 21.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Drug Development*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Mental Disorders / drug therapy
  • Mental Disorders / enzymology
  • Nervous System Diseases / drug therapy
  • Nervous System Diseases / enzymology
  • Patents as Topic
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / metabolism

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • AAK1 protein, human
  • Protein Serine-Threonine Kinases