Muvalaplin

Muvalaplin is an investigational new drug that is being evaluated in clinical trials for the treatment of cardiovascular disease associated with elevated lipoprotein(a) levels.^[1][2] It is an orally bioavailable small molecule drug that blocks the initial interaction between apolipoprotein(a) and apoB100, thereby preventing the assembly of new lipoprotein(a) particles without interfering with plasminogen function. Large-scale studies are underway to assess muvalaplin’s safety and efficacy for reducing cardiovascular risk in people with high levels of lipoprotein(a).^[1]

Muvalaplin

Clinical data
Other names	LY3473329
Identifiers
IUPAC name (2S)-3-[3-[[bis[[3-[(2S)-2-carboxy-2-[(3R)-pyrrolidin-3-yl]ethyl]phenyl]methyl]amino]methyl]phenyl]-2-[(3R)-pyrrolidin-3-yl]propanoic acid
CAS Number	2565656-70-2
PubChem CID	155369486
IUPHAR/BPS	12939
ChemSpider	129341115
UNII	HSU2KY4EFK
KEGG	D12460
ChEMBL	ChEMBL4802585
PDB ligand	A1AAK (PDBe, RCSB PDB)
Chemical and physical data
Formula	C42H54N4O6
Molar mass	710.916 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1CNC[C@H]1[C@H](CC2=CC(=CC=C2)CN(CC3=CC=CC(=C3)C[C@@H]([C@H]4CCNC4)C(=O)O)CC5=CC=CC(=C5)C[C@@H]([C@H]6CCNC6)C(=O)O)C(=O)O
InChI InChI=InChI=1S/C42H54N4O6/c47-40(48)37(34-10-13-43-22-34)19-28-4-1-7-31(16-28)25-46(26-32-8-2-5-29(17-32)20-38(41(49)50)35-11-14-44-23-35)27-33-9-3-6-30(18-33)21-39(42(51)52)36-12-15-45-24-36/h1-9,16-18,34-39,43-45H,10-15,19-27H2,(H,47,48)(H,49,50)(H,51,52)/t34-,35-,36-,37-,38-,39-/m0/s1 Key:BRLGERLDHZRETI-BGBFCPIGSA-N

Chemistry

Muvalaplin is a synthetic trivalent small molecule built around a central tribenzylamine scaffold. Attached to this core are three identical arms, each consisting of a (S)-2-[(3R)-pyrrolidin-3-yl]propanoic acid moiety. The molecule’s tripodal configuration enables simultaneous engagement of multiple lysine-binding sites on the apo(a) kringle domains, which is essential for potent inhibition of lipoprotein(a) assembly.^[3]