2455427-91-3

Product Details:

CasNo： 2455427-91-3

Molecular Formula： C20H20F2N6O2

Appearance： Almost white to yellowish white

Packing： Aluminium bag

Throughput： 100KG/Month

Purity： 99%

Laroprovstat, code name AZD0780, is an investigational oral small‑molecule PCSK9 inhibitor discovered by Dogma Therapeutics and developed by AstraZeneca, currently in Phase III clinical development for lipid‑lowering therapy.NIHR Innov...

Basic Information

• INN: Laroprovstat
• Code: AZD0780
• Class: Antihyperlipidaemic agent, oral PCSK9 inhibitor
• Form: Film‑coated tablet
• Route of administration: Oral, once daily
• Status: Not yet approved; Phase III ongoing
• Originator: Dogma Therapeutics; License / Developer: AstraZeneca

Mechanism of Action

Unlike injectable PCSK9 monoclonal antibodies that block PCSK9 binding to LDL receptor directly, laroprovstat binds selectively to a novel pocket on the C‑terminal domain of PCSK9. It stabilizes the PCSK9 structure and prevents lysosomal trafficking and degradation of the PCSK9–LDLR complex, thereby preserving and recycling hepatic LDL receptors to clear circulating LDL‑C. It does not disrupt the initial binding between PCSK9 and LDLR.NIHR Innov...

Indications (Proposed)

For management of adult patients with:

• Primary hypercholesterolaemia
• Mixed dyslipidaemia
• Established atherosclerotic cardiovascular disease (ASCVD), or patients at risk of a first ASCVD event
• Heterozygous familial hypercholesterolaemia (HeFH), as add‑on therapy when statin monotherapy fails to achieve LDL‑C targetsNIHR Innov...

Key Pharmacology

• Half‑life: Approximately 40 hours, supporting once‑daily dosing
• Oral bioavailability: 78.4%
• Food effect: Minimal; absorption is not meaningfully affected by high‑fat meals
• Metabolism: Predominantly metabolized by CYP3A (~90%)
• Dose‑proportional PK profile

Clinical Efficacy Highlights

In Phase 1 clinical data:

• As monotherapy, laroprovstat reduced LDL‑C by roughly 30–38% at tested doses.
• When added on top of rosuvastatin 20 mg, the combination achieved up to ~78% LDL‑C reduction from baseline in hypercholesterolaemic subjects; some cohorts reported up to 80% total LDL‑C lowering in statin‑naïve patients.
• Favourable safety and tolerability profile in early trials, with low frequency of serious adverse events.Oxford Aca...

Commercial & Technical Advantage

Existing marketed PCSK9 inhibitors are injectable antibodies. Laroprovstat is one of the most advanced oral small‑molecule PCSK9 candidates, offering patients a convenient oral alternative for long‑term LDL‑C control and cardiovascular risk reduction. It is being evaluated both as monotherapy and for potential fixed‑dose combination with statins.

Disclaimer

Laroprovstat is an investigational drug. No marketing authorization has been granted by FDA, EMA or other regulatory authorities at present. All data herein are extracted from public clinical trial and scientific publications, not from an approved SmPC.