CNP (C-type Natriuretic Peptide)

Cardiovascular / Bone Growth

Also known as: C-type Natriuretic Peptide, CNP-22, CNP-53, NPPC

Natriuretic PeptidesResearch phase: Endogenous hormone (well characterized)Regulatory: Endogenous peptide. Vosoritide (CNP analog) is FDA-approved for achondroplasia. CNP itself is not used clinically.

Mechanism

CNP is the third natriuretic peptide, but unlike ANP and BNP, it is mainly produced in blood vessels and the brain rather than the heart. Its most important role is stimulating bone growth at growth plates — CNP deficiency causes short stature, while excess causes overgrowth. Vosoritide (a CNP analog) is FDA-approved for achondroplasia based on this mechanism. CNP also has vasodilatory and anti-fibrotic effects.

Technical detail

CNP exists as CNP-53 (predominant in tissues) and CNP-22 (processed form), both derived from the NPPC gene. Unlike ANP/BNP, CNP signals through NPR-B (GC-B, natriuretic peptide receptor B), generating cGMP-PKG signaling. In growth plate chondrocytes, CNP-NPR-B-cGMP-PKG II signaling antagonizes FGFR3-MAPK (Ras-Raf-MEK-ERK) pathway inhibition of chondrocyte proliferation and differentiation, rescuing endochondral ossification. FGFR3 gain-of-function (achondroplasia) is counteracted by CNP-mediated inhibition of RAF1 phosphorylation. Vascular CNP activates NPR-B on smooth muscle for vasodilation and NPR-C-Gi for anti-proliferative effects. CNP is cleared by neprilysin and NPR-C.

Evidence

Once-Weekly Navepegritide in Children With Achondroplasia: The APPROACH Randomized Clinical Trial
Savarirayan et al. (2026) — JAMA Pediatrics — PMID: 41247754
Once-weekly navepegritide, an investigational C-type natriuretic peptide prodrug, demonstrated efficacy and tolerability in children with achondroplasia, supporting sustained therapeutic relevance of the CNP pathway.
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Vosoritide therapy in children with achondroplasia aged 3-59 months: a multinational, randomised, double-blind, placebo-controlled, phase 2 trial
Savarirayan et al. (2024) — The Lancet Child & Adolescent Health — PMID: 37984383
In infants and young children with achondroplasia, vosoritide showed acceptable safety and improved height-related outcomes, extending CNP-pathway clinical evidence into younger age groups.
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Once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial
Savarirayan et al. (2020) — Lancet — PMID: 32891212
Vosoritide, a C-type natriuretic peptide analogue, increased annualized growth velocity in children with achondroplasia over 52 weeks in a multicenter placebo-controlled phase 3 trial.
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