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Review
. 2022 Jun 3;11(6):859.
doi: 10.3390/biology11060859.

Natriuretic Peptide-Based Novel Therapeutics: Long Journeys of Drug Developments Optimized for Disease States

Tomoko Ichiki  1 , Atsushi Jinno  1 , Yoshihisa Tsuji  1
Affiliations
Review

Natriuretic Peptide-Based Novel Therapeutics: Long Journeys of Drug Developments Optimized for Disease States

Tomoko Ichiki et al. Biology (Basel). .

Abstract

The field of natriuretic peptides (NPs) as an endocrine hormone has been developing since 1979. There are three peptides in humans: atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), which bind to the guanylyl cyclase-A (GC-A) receptor (also called natriuretic peptide receptor-A (NPR-A)), and C-type natriuretic peptide (CNP), which binds to the GC-B receptor (also called the NPR-B) and then synthesizes intracellular cGMP. GC-A receptor stimulation has natriuretic, vasodilatory, cardiorenal protective and anti-renin-angiotensin-aldosterone system actions, and GC-B receptor stimulation can suppress myocardial fibrosis and can activate bone growth before epiphyseal plate closure. These physiological effects are useful as therapeutics for some disease states, such as heart failure, hypertension, and dwarfism. To optimize the therapeutics for each disease state, we must consider drug metabolism, delivery systems, and target receptor(s). We review the cardiac NP system; new designer NPs, such as modified/combined NPs and modified peptides that can bind to not only NP receptors but receptors for other systems; and oral drugs that enhance endogenous NP activity. Finally, we discuss prospective drug discoveries and the development of novel NP therapeutics.

Keywords: dwarfism; heart failure; hypertension; natriuretic peptides.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Native natriuretic peptides in human. DPPIV, dipeptidyl peptidase-4; GC-A, guanylyl cyclase-A; GC-B, guanylyl cyclase-B; IDE, insulin degrading enzyme; NEP, neprilysin; NPR-A, natriuretic peptide receptor A; NPR-B, natriuretic peptide receptor B; NPR-C, natriuretic peptide receptor C; RAAS, renin–angiotensin–aldosterone system.
Figure 2
Figure 2
Designer NPs: Modified or combination of NPs. DNP, Dendroaspis natriuretic peptide; GC-A, guanylyl cyclase-A; GC-B, guanylyl cyclase-B.
Figure 3
Figure 3
Designer NPs: Combination of NP and peptide from other systems. AA, amino acid; Ang1–7, angiotensin1–7, GC-A, guanylyl cyclase-A, GC-B, guanylyl cyclase-B; MasR, Mas receptor; RAAS, renin-angiotensin-aldosterone system.
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