First-in-Human Study of MANP: A Novel ANP (Atrial Natriuretic Peptide) Analog in Human Hypertension

Horng H. Chen, Siu Hin Wan, Seethalakshmi R. Iyer, Valentina Cannone, S. Jeson Sangaralingham, Joel Nuetel, John C. Burnett

Research output: Contribution to journalArticlepeer-review


M-atrial natriuretic peptide (MANP) is a novel ANP (atrial natriuretic peptide) analog engineered to be an innovative particulate GC-A (guanylyl cyclase A) receptor activator. The rationale for its design was to develop a best-in-class GC-A activator with enhanced cGMP activating, natriuretic, aldosterone-suppressing, and blood pressure-lowering actions, compared with endogenous ANP, for the treatment of hypertension. Here, we report the first-in-human study on the safety, tolerability, neurohumoral, renal, and blood pressure-lowering properties of MANP in hypertension subjects. This was an open-label sequential single ascending dose design in which all subjects stopped all antihypertensive agents for 14 days before receiving a single subcutaneous injection of MANP. MANP was safe, well tolerated, activated cGMP, induced natriuresis, reduced aldosterone, and decreased blood pressure at or below the maximal tolerated dose. Thus, MANP has a favorable safety profile and produced expected pharmacological effects in human hypertension. Our results support further investigations of MANP as a potential future blood pressure-lowering, natriuretic and aldosterone-suppressing drug for hypertension especially resistant hypertension.

Original languageEnglish (US)
Pages (from-to)1859-1867
Number of pages9
Issue number6
StatePublished - Dec 1 2021


  • aldosterone
  • blood pressure
  • cardiovascular disease
  • guanylyl cyclase
  • natriuresis

ASJC Scopus subject areas

  • Internal Medicine


Dive into the research topics of 'First-in-Human Study of MANP: A Novel ANP (Atrial Natriuretic Peptide) Analog in Human Hypertension'. Together they form a unique fingerprint.

Cite this