NPRA agonists, compositions, and uses thereof
This disclosure provides a natriuretic peptide derivative of Formula (I), and to compositions including a natriuretic peptide derivative of Formula (I), (fatty acyl) z -(B) x -(G) y -NP (I), wherein: z is 1, x is an integer from 2 to 4 and y is 3; or z is 0, x is an integer from 0 to 4 and y is an integer from 1 to 3; fatty acyl comprises from 12 to 24 (e.g., 12 to 18) carbons atoms; B is lysine or arginine; G is glycine; NP is a natriuretic peptide; if present, (fatty acyl) z - is covalently linked to the N-terminus of (B) x ; (fatty acyl) z -(B) x — is covalently linked to the N-terminus of (G) y ; and (fatty acyl) z -(B) x -(G) y - is covalently linked to the N-terminus of NP. The natriuretic peptide derivative according to the disclosure, and compositions thereof, are useful in the treatment of diseases such as hypertension, vascular congestion, and heart disease.
1 . A composition comprising a natriuretic peptide derivative, wherein the natriuretic peptide derivative comprises SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 14, SEQ ID NO: 18, SEQ ID NO: 52, SEQ ID NO: 56, SEQ ID NO: 68, SEQ ID NO: 72, SEQ ID NO: 86, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 113, or SEQ ID NO: 122.
2 . The composition according to claim 1 , wherein the natriuretic peptide derivative is selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 14, SEQ ID NO: 18, SEQ ID NO: 56, SEQ ID NO: 52, SEQ ID NO: 113, SEQ ID NO: 68, SEQ ID NO: 122, and SEQ ID NO: 72.
3 . The composition according to claim 1 , wherein the natriuretic peptide derivative is selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 14, SEQ ID NO: 18, SEQ ID NO: 56, and SEQ ID NO: 72.
4 . The composition according to claim 1 , wherein the natriuretic peptide derivative is selected from the group consisting of SEQ ID NO: 14, SEQ ID NO: 18, SEQ ID NO: 56, SEQ ID NO: 52, SEQ ID NO: 68, SEQ ID NO: 122, and SEQ ID NO: 72.
5 . The composition according to claim 1 , further comprising an excipient.
6 . The composition of claim 1 , wherein the natriuretic peptide derivative is, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 14, SEQ ID NO: 18, SEQ ID NO: 52, SEQ ID NO: 56, SEQ ID NO: 68, SEQ ID NO: 72, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 113, or SEQ ID NO: 122.
7 . A method of increasing blood cGMP in a patient, the method comprising parenterally administering to the patient a composition according to claim 1 .