Pharmacodynamics of a novel designer natriuretic peptide, CD-NP, in a first-in-human clinical trial in healthy subjects.
CD-NP is a novel chimeric natriuretic peptide (NP) consisting of the 22-amino-acid (AA) human C-type natriuretic peptide (CNP), a venodilating peptide with limited renal actions and minimal effects on blood pressure, and the 15-AA C-terminus of Dendroaspis NP (DNP). The rationale for the design of CD-NP was to enhance the renal actions of CNP, the ligand for natriuretic peptide receptor-B, but without inducing excessive hypotension. Here we report the first-in-human studies for CD-NP, which represent the first successful clinical testing of a chimeric NP demonstrating in normal human volunteers that CD-NP possesses cyclic guanosine monophosphate-activating, natriuretic, and aldosterone-suppressing properties without inducing excessive hypotension, laying the foundation for additional studies on this first-in-class new cardiovascular therapeutic in human heart failure, which are now underway worldwide.
Lee
Candace Y W
CY
Cardiorenal Research Laboratory, Guggenheim 915, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA.
Chen
Horng H
HH
Lisy
Ondrej
O
Swan
Suzanne
S
Cannon
Courtney
C
Lieu
Hsiao D
HD
Burnett
John C
JC
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D015195:Drug Design; D004546:Elapid Venoms / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D020098:Natriuretic Peptide, C-Type / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D012964:Sodium / Q000652:urine
C542600:CD-NP natriuretic peptide; D002317:Cardiovascular Agents; D004546:Elapid Venoms; D011993:Recombinant Fusion Proteins; D020098:Natriuretic Peptide, C-Type; D012964:Sodium; D006152:Cyclic GMP