| Description | Muvalaplin (LY3473329) is an orally active lipoprotein (a) Lp(a) reagent that inhibits Lp(a) formation by blocking apo(a)-apo B100 interactions. |
| In vivo | 单次递增剂量治疗评估了健康参与者单次服用Muvalaplin（剂量范围从1 mg到800 mg）或安慰剂对任意Lp(a)水平的影响。多次递增剂量治疗则评估了连续每日服用Muvalaplin（30 mg至800 mg）或安慰剂14天，在Lp(a)水平高于30 mg/dL的患者中的影响。口服30 mg至800 mg的Muvalaplin连续14天，导致其在血浆中的浓度及半衰期显著增加，范围从70小时至414小时。Muvalaplin在首次剂量后24小时内降低了Lp(a)血浆水平，并在重复给药时进一步降低了Lp(a)水平。最大的安慰剂校正Lp(a)降低率为63%至65%，使93%的参与者的Lp(a)血浆水平降至50 mg/dL以下，每日剂量100 mg或以上时效果相似。未观察到凝血酶原水平或活性的临床意义上的变化。结论：作为一种选择性的小分子Lp(a)形成抑制剂，Muvalaplin未引起耐受性问题，并在连续每日给药14天后将Lp(a)水平降低至多65%。 |
| Synonyms | LY3473329 |
| molecular weight | 710.9 |
| Molecular formula | C42H54N4O6 |
| CAS | 2565656-70-2 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 10 mg/mL (14.07 mM), when pH is adjusted to 6. Sonication is recommended. H2O: <0.1 mg/mL |
| 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. 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. |