| Chemical Properties | Back Directory | [Boiling point ]
863.9±60.0 °C(Predicted) | [density ]
1.234±0.06 g/cm3(Predicted) | [solubility ]
PBS (pH 7.2): Slightly Soluble: 0.1-1 mg/ml | [form ]
Solid | [pka]
3.79±0.10(Predicted) | [color ]
Off-white to light yellow | [InChIKey]
BRLGERLDHZRETI-BGBFCPIGSA-N | [SMILES]
[C@H]([C@]1([H])CNCC1)(C(=O)O)CC1C=CC=C(C=1)CN(CC1C=CC=C(C=1)C[C@@H]([C@]1([H])CNCC1)C(=O)O)CC1C=CC=C(C=1)C[C@@H]([C@]1([H])CNCC1)C(=O)O |
| Hazard Information | Back Directory | [Uses]
Muvalaplin (LY3473329) is an orally active, selective small molecule inhibitor of lipoprotein (a) (Lp (a)) that disrupts the initial non-covalent interaction between apo(a) and apoB100, preventing the disulphide bond and Lp(a)
formation. Muvalaplin reduces the levels of Lp (a) in transgenic mice and in cynomolgus monkeys[1][2][3][4][5]. | [in vivo]
Muvalaplin (1-30 mg/kg, p.o., daily for 5 days) reduces the levels of Lp(a) in the Lp (a) transgenic mouse model[3].
Muvalaplin (1-100 mg/kg, p.o., daily for 15 days) reduces the levels of Lp (a) levels in cynomolgus monkeys[3].
| Animal Model: | Lp (a) transgenic mouse model[3] | | Dosage: | 1-30 mg/kg | | Administration: | p.o., daily for 5 days | | Result: | Reduced the levels of Lp(a) with an absolute ED50 of 3?mg/kg. |
| Animal Model: | Cynomolgus monkeys[3] | | Dosage: | 1-100 mg/kg | | Administration: | p.o., daily for 15 days | | Result: | Reduced median Lp(a) levels in a dose-dependent manner by up to 71%. |
| [References]
[1] Bhatia HS, et al. Lipoprotein(a): Evidence for Role as a Causal Risk Factor in Cardiovascular Disease and Emerging Therapies. J Clin Med. 2022 Oct 13;11(20):6040. DOI:10.3390/jcm11206040
[2] Nicholls SJ, et al. Muvalaplin, an Oral Small Molecule Inhibitor of Lipoprotein(a) Formation: A Randomized Clinical Trial. JAMA. 2023 Sep 19;330(11):1042-1053. DOI:10.1001/jama.2023.16503
[3] Diaz N, et al. Discovery of potent small-molecule inhibitors of lipoprotein(a) formation. Nature. 2024 May;629(8013):945-950. DOI:10.1038/s41586-024-07387-z
[4] Hooper AJ, et al. Potential of muvalaplin as a lipoprotein(a) inhibitor. Expert Opin Investig Drugs. 2024 Jan;33(1):5-7. DOI:10.1080/13543784.2024.2302592
[5] Norata GD, et al. Oral strategies to target proprotein convertase subtilisin/kexin type 9 and lipoprotein(a): the new frontier of lipid lowering. Eur Heart J. 2023 Dec 21;44(48):5018-5020. DOI:10.1093/eurheartj/ehad682 |
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