Muvalaplin

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;

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]

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]

References

^ ^a ^b De Los Reyes C, Rikhi RR, Doherty S, Hernandez S, Mirzai S, Shapiro MD, et al. (December 2025). "Current Clinical Trials for Treating Elevated Lipoprotein(a)". Current Cardiovascular Risk Reports. 19 (1) 7. doi:10.1007/s12170-025-00759-8. PMC 12282488. PMID 40703143.
^ Hooper AJ, Fernando PM, Burnett JR (January 2024). "Potential of muvalaplin as a lipoprotein(a) inhibitor". Expert Opinion on Investigational Drugs. 33 (1): 5–7. doi:10.1080/13543784.2024.2302592. PMID 38186354.
^ Diaz N, Perez C, Escribano AM, Sanz G, Priego J, Lafuente C, et al. (May 2024). "Discovery of potent small-molecule inhibitors of lipoprotein(a) formation". Nature. 629 (8013): 945–950. Bibcode:2024Natur.629..945D. doi:10.1038/s41586-024-07387-z. PMC 11111404. PMID 38720069.

[De_Los_Reyes_2025-1] De Los Reyes C, Rikhi RR, Doherty S, Hernandez S, Mirzai S, Shapiro MD, et al. (December 2025). "Current Clinical Trials for Treating Elevated Lipoprotein(a)". Current Cardiovascular Risk Reports. 19 (1) 7. doi:10.1007/s12170-025-00759-8. PMC 12282488. PMID 40703143.

[Hooper_2024-2] Hooper AJ, Fernando PM, Burnett JR (January 2024). "Potential of muvalaplin as a lipoprotein(a) inhibitor". Expert Opinion on Investigational Drugs. 33 (1): 5–7. doi:10.1080/13543784.2024.2302592. PMID 38186354.

[Diaz_2024-3] Diaz N, Perez C, Escribano AM, Sanz G, Priego J, Lafuente C, et al. (May 2024). "Discovery of potent small-molecule inhibitors of lipoprotein(a) formation". Nature. 629 (8013): 945–950. Bibcode:2024Natur.629..945D. doi:10.1038/s41586-024-07387-z. PMC 11111404. PMID 38720069.

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