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Clark AJ, Forfar R, Hussain M, et al. ACTH Antagonists. Front Endocrinol (Lausanne). 2016;7:101doi: 10.3389/fendo.2016.00101.
Clark, A. J., Forfar, R., Hussain, M., Jerman, J., McIver, E., Taylor, D., & Chan, L. (2016). ACTH Antagonists. Frontiers in endocrinology, 7101. https://doi.org/10.3389/fendo.2016.00101
Clark, Adrian John, et al. "ACTH Antagonists." Frontiers in endocrinology vol. 7 (2016): 101. doi: https://doi.org/10.3389/fendo.2016.00101
Clark AJ, Forfar R, Hussain M, Jerman J, McIver E, Taylor D, Chan L. ACTH Antagonists. Front Endocrinol (Lausanne). 2016 Aug 05;7:101. doi: 10.3389/fendo.2016.00101. eCollection 2016. PMID: 27547198; PMCID: PMC4974254.
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Front Endocrinol (Lausanne). 2016 Aug 05;7:101. doi: 10.3389/fendo.2016.00101. eCollection 2016.

ACTH Antagonists.

Frontiers in endocrinology

Adrian John Clark, Rachel Forfar, Mashal Hussain, Jeff Jerman, Ed McIver, Debra Taylor, Li Chan

Affiliations

  1. Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London , London , UK.
  2. Centre for Therapeutics Discovery, MRC Technology , Stevenage , UK.

PMID: 27547198 PMCID: PMC4974254 DOI: 10.3389/fendo.2016.00101

Abstract

Adrenocorticotropin (ACTH) acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R), is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP) for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1) Cushing's disease and ectopic ACTH syndrome - especially while preparing for definitive treatment of a causative tumor, or in refractory cases, or (2) congenital adrenal hyperplasia - as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article, we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role.

Keywords: Cushing’s syndrome; G protein-coupled receptor; adrenocorticotropin hormone; congenital adrenal hyperplasia; high throughput screening; peptide hormone antagonists; receptor antagonism; receptor modelling

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