ASB20123: A novel C-type natriuretic peptide derivative for treatment of growth failure and dwarfism

PloS One
Naomi MorozumiKenji Kangawa

Abstract

C-type natriuretic peptide (CNP) and its receptor natriuretic peptide receptor B (NPR-B) are physiological potent positive regulators of endochondral bone growth; therefore, the CNP/NPR-B signaling pathway is one of the most promising therapeutic targets for treating growth failure and dwarfism. In this article, we summarized the pharmacological properties of a novel CNP analog peptide ASB20123 as a therapeutic agent for short stature. ASB20123, one of the CNP/ghrelin chimeric peptides, is composed of CNP(1-22) and human ghrelin(12-28, E17D). Compared to CNP(1-22), ASB20123 showed similar agonist activity for NPR-B and improved biokinetics with a longer plasma half-life in rats. In addition, the distribution of ASB20123 to the cartilage was higher than that of CNP(1-22) after single subcutaneous (sc) injection to mice. These results suggested that the C-terminal part of ghrelin, which has clusters of basic amino acid residues and a BX7B motif, might contribute to the retention of ASB20123 in the extracellular matrix of the growth plate. Multiple sc doses of ASB20123 potently stimulated skeletal growth in rats in a dose-dependent manner, and sc infusion was more effective than bolus injection at the same dose. Our data indicated...Continue Reading

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Citations

Dec 4, 2019·Current Opinion in Endocrinology, Diabetes, and Obesity·Juanita K Hodax, Sara A DiVall
Jan 28, 2021·International Journal of Molecular Sciences·Samantha M MirczukRobert C Fowkes
Mar 31, 2021·JCI Insight·Brandon M WagnerLincoln R Potter
Dec 6, 2021·Osteoarthritis and Cartilage·B FafilekP Krejci

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Methods Mentioned

BETA
amino acid exchange
enzyme-linked immunosorbent assay
ELISA

Software Mentioned

FlexStation

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