Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly

JJ Kopchick, C Parkinson, EC Stevens… - Endocrine …, 2002 - academic.oup.com
JJ Kopchick, C Parkinson, EC Stevens, PJ Trainer
Endocrine reviews, 2002academic.oup.com
An understanding of the events that occur during GH receptor (GHR) signaling has
facilitated the development of a GHR antagonist (pegvisomant) for use in humans. This
molecule has been designed to compete with native GH for the GHR and to prevent its
proper or functional dimerization—a process that is critical for GH signal transduction and
IGF-I synthesis and secretion. Clinical trials in patients with acromegaly show GHR blockade
to be an exciting new mode of therapy for this condition, and pegvisomant may have a …
Abstract
An understanding of the events that occur during GH receptor (GHR) signaling has facilitated the development of a GHR antagonist (pegvisomant) for use in humans. This molecule has been designed to compete with native GH for the GHR and to prevent its proper or functional dimerization—a process that is critical for GH signal transduction and IGF-I synthesis and secretion. Clinical trials in patients with acromegaly show GHR blockade to be an exciting new mode of therapy for this condition, and pegvisomant may have a therapeutic role in diseases, such as diabetes and malignancy, in which abnormalities of the GH/IGF-I axis have been observed. This review charts the discovery and development of GHR antagonists and details the experience gained in patients with acromegaly.
Oxford University Press