Cyclic polypeptides for pcsk9 inhibition
AssigneeRa Pharmaceuticals, Inc.
InventorsAlonso Ricardo, Nicolas Cedric Boyer, Joseph R. Stringer, Derek M. LaPlaca, Kelli Jette, Yili Sun
Life of this patent
Estimating the term…
Abstract
Provided herein are cyclic polypeptide compounds that can, e.g., bind specifically to human proprotein convertase subtilisin/kexin type 9 (PCSK9) and optionally also inhibit interaction between human PCSK9 and human low density lipoprotein receptor (LDLR), and pharmaceutical compositions comprising one or more of these compounds. Also provided are methods of reducing LDL cholesterol level in a subject in need thereof that include administering to the subject one or more of the cyclic polypeptide compounds or a pharmaceutical composition provided herein.
Claims19
A polycyclic peptide of Formula (I):
- or a pharmaceutically acceptable salt thereof;
- wherein:
- A1 is H or an acyl protected amine;
- R1 is selected from the group consisting of the amino acid side chains of ALA, GLY, ACB, ACPE, APC, LYS, NVA, PRO, and TBG;
- R2 is selected from the group consisting of the amino acid side chains of ALA and GLY;
- R3 is selected from the group consisting of the amino acid side chains of 4SFPRO, AIB, AZE, 4RFPRO, DHPRO, 4DFPRO, PIP, PRO, HSE, SISQ, and RISQ;
- R4 is selected from the group consisting of the amino acid side chains of ALA, HIS, GLY, and PRO;
- R5 is selected from the group consisting of the amino acid side chains of TYR, 4CF, 4FF, MFF, CNPP, 2NA, 1NA, F3MF, PHE, PRO, and OMY;
- A2 is absent or
- and
- P1 is selected from the group consisting of H and acetyl;
- wherein each amino acid residue is optionally an N-methylated amino acid;
- wherein each amino acid residue can be the R or S-enantiomer configuration.
A cyclic peptide compound:
- 001, 003, 004, 005, 006, 007, 008, 009, 010, 011, 012, 013,
- 014, 015, 016, 017, 018, 019, 020, 021, 022, 023, 024, 025, 026, 027, 028, 042, 043, 044, 045, 04 6, 049, 055, 056, 059, 060, 067, 072, 073, 074, 075, 076, 077, 078, 079, 080, 090, 096, 097, 098, 099, 100, 101, 102, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 118, 119, or 120.
A cyclic peptide compound:
- 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, or 131.
Dependencies are inferred from the claim text.