预约演示
更新于：2026-09-04
Laroprovstat
更新于：2026-09-04
概要
基本信息
原研机构 |
非在研机构- |
权益机构- |
最高研发阶段临床3期 |
首次获批日期- |
最高研发阶段(中国)临床3期 |
特殊审评- |
登录后查看时间轴
结构/序列
分子式C20H20F2N6O2 |
InChIKeyNCHUWRLOTSAFFN-KBPBESRZSA-N |
CAS号2455427-91-3 |
关联
21
项与 Laroprovstat 相关的临床试验NCT07619118
A Phase III Randomised, Double-Blind, Parallel-Group Study to Assess the Effect of Fixed Dose Combination Laroprovstat/Rosuvastatin Compared With Rosuvastatin on Low-Density Lipoprotein Cholesterol in Patients With Hypercholesterolaemia
NCT07619131
A Phase III Randomised, Double-Blind, Factorial Design Study to Assess the Effect of Fixed Dose Combination Laroprovstat/Rosuvastatin Compared With Laroprovstat, Rosuvastatin, and Placebo on Low-Density Lipoprotein Cholesterol in Lipid-Lowering Treatment-Naïve Patients
NCT07622433
A Phase I, Randomized, Open-label, 4-period, 4-treatment, Single-dose, Cross-over Study to Assess the Relative Bioavailability of Laroprovstat/Ezetimibe Fixed Combination Drug Products to the Single Therapy Products in Healthy Adults
100 项与 Laroprovstat 相关的临床结果
登录后查看更多信息
100 项与 Laroprovstat 相关的转化医学
登录后查看更多信息
100 项与 Laroprovstat 相关的专利（医药）
登录后查看更多信息
7
项与 Laroprovstat 相关的文献（医药）2026-06-23CIRCULATION
Laroprovstat, the First Oral Small-Molecule PCSK9 Inhibitor for the Treatment of Hypercholesterolemia: Results From a Randomized, Single-Blind, Placebo-Controlled Phase 1 Trial in Treatment-Naïve Patients
Article
作者: Rosenmeier, Jaya B. ; Gutgsell, Aspen ; Garkaviy, Pavlo ; Ahnmark, Andrea ; Barbour, April M. ; Kaushik, Virendar ; Lindén, Daniel ; Hober, Andreas ; O’Mahony, Gavin ; Yu, Hongtao ; Hubbard, Brian ; Knöchel, Jane ; Bogstedt, Anna ; Underwood, Christina Rye ; Geschwindner, Stefan ; Töppner Carlsson, Eva ; Twaddle, Lee ; Serrano-Wu, Michael ; Bergenholm, Linnéa ; Brengdahl, Johan ; Ryaboshapkina, Maria ; Hurt-Camejo, Eva ; Carter, Debra ; Rudvik, Anna ; McCarthy, Michael C. ; Vega, Rick B. ; Miliotis, Tasso ; Laru, Johanna ; Hochdörfer, Thomas
BACKGROUND::
Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) is an effective therapy for reducing low-density lipoprotein (LDL) cholesterol (LDL-C) in adults with hyperlipidemia, including heterozygous familial hypercholesterolemia, thereby lowering cardiovascular risk. Current PCSK9 inhibitors are injectable therapies; no oral small-molecule PCSK9 inhibitor has yet been approved.
METHODS::
Laroprovstat (AZD0780) is a novel small-molecule identified through structure-based design that binds to the PCSK9 C-terminal domain. The effects of laroprovstat on LDL receptor expression and LDL-C levels were assessed in vitro and in mice expressing human
PCSK9
. Safety, tolerability, and pharmacokinetic and pharmacodynamic properties of laroprovstat were assessed in healthy participants with LDL-C ≥70 and ≤190 mg/dL after single ascending doses. Laroprovstat was also assessed in participants with LDL-C ≥100 and ≤190 mg/dL at doses of 1 mg or 30 mg versus placebo administered once daily for 28 days after a rosuvastatin 20 mg run-in treatment period.
RESULTS::
Laroprovstat does not inhibit the PCSK9–LDL receptor interaction but stabilizes the PCSK9 C-terminal domain, preventing lysosomal trafficking and degradation of LDL receptor. Laroprovstat increased LDL receptor expression and reduced LDL-C levels in mice expressing human
PCSK9
. Laroprovstat displayed dose-proportional pharmacokinetics and a half-life suitable for once-daily dosing (≈40 hours). There was no clinically meaningful change in exposure when dosed with a high-fat meal compared with the fasted state (area under the plasma concentration-time curve
inf
and C
max
geometric mean reduction of 1.15 [90% CI, 1.11–1.19] and 1.06 [90% CI, 1.00–1.13], respectively). After a rosuvastatin 20 mg 3-week run-in treatment period, laroprovstat 1 and 30 mg reduced LDL-C by 29% (95% CI, 18%–38%) and 51% (95% CI, 44%–58%) compared with baseline. Combined rosuvastatin and laroprovstat treatment resulted in a total approximate reduction in LDL-C of 70% and 80% for laroprovstat 1 and 30 mg, respectively.
CONCLUSIONS::
Laroprovstat was well tolerated with no safety findings of concern and may be dosed with or without food. In treatment-naïve participants with hypercholesterolemia, combined rosuvastatin 20 mg and laroprovstat 30 mg treatment led to an 80% LDL-C reduction, supporting further development of laroprovstat as the first oral small-molecule PCSK9 inhibitor in patients with hypercholesterolemia.
REGISTRATION::
URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT05384262.
2026-02-01JOURNAL OF CLINICAL PHARMACOLOGY
Pharmacokinetics, Disposition, and Biotransformation of Laroprovstat in Humans: In Vivo and In Vitro Evaluations
Article
作者: Rosenmeier, Jaya ; Vedin‐Nilsson, Charlotta ; Karlsson, Isabella Bonner ; Reinen, Jelle ; Li, Xue‐Qing ; Vega, Rick ; Panduga, Vijender ; Barbour, April M. ; Tanner, Lloyd ; Rudvik, Anna ; Elebring, Marie ; Pelay‐Gimeno, Marta ; Simmonds, Rebecca ; Nilsson, Catarina ; Heijer, Maria ; Singh, Nand
Abstract:
Laroprovstat (AZD0780) is a small‐molecule, oral PCSK9 inhibitor being developed for hypercholesterolemia. In vitro experiments and a two‐part clinical study were conducted to characterize laroprovstat routes of elimination, metabolism, and absolute oral bioavailability. Laroprovstat was incubated in human hepatic spheroids from two different donors with and without ketoconazole to examine metabolite formation. A clinical study was conducted in eight healthy male participants, whereby in Part 1 each subject received a single oral dose of 60 mg as tablets of laroprovstat with a 100‐µg IV infusion of [
14
C]laroprovstat solution to determine absolute oral bioavailability. In Part 2, a single oral dose of 60‐mg [
14
C]laroprovstat solution was administered for disposition and biotransformation characterization. Based on in vitro studies, CYP3A are the predominant enzymes involved in the oxidative metabolism of laroprovstat, accounting for approximately 90% of laroprovstat metabolism. From the clinical study, laroprovstat is highly orally bioavailable, 78.4%. Laroprovstat was extensively metabolized with most of the dose excreted as oxidative metabolites with some additional conjugation. Only 15% and 6% of the dose was eliminated as parent in the urine and feces, respectively. No major circulating metabolites were identified that require further safety assessment or in vitro evaluation of DDI potential, aligned with the analysis of metabolites in plasma after repeated administration of laroprovstat from the MAD study. Renal elimination of total radioactivity was 64%, compared to 26% in the feces. Laroprovstat does not undergo significant chiral interconversion. Laroprovstat was well tolerated with no new safety concerns. These studies successfully characterized the ADME properties of laroprovstat.
2025-12-01Current Atherosclerosis Reports
Oral PCSK9 Inhibitors: Will They Work?
Review
作者: Lale Tokgözoğlu ; Alberico L. Catapano ; Angela Pirillo
PURPOSE OF REVIEW:
Lowering low-density lipoprotein cholesterol (LDL-C) is a crucial step in reducing the risk of atherosclerotic cardiovascular disease. Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9), an important regulator of circulating LDL-C levels, represent a modern approach for the treatment of hypercholesterolaemia. Approved approaches targeting PCSK9 to date include injectable biologics. Here, we provide an overview of the current state of research on the development of oral PCSK9 inhibitors.
RECENT FINDINGS:
Several small molecules have been developed in recent years. Enlicitide decanoate (formerly known as MK-0616) has been shown to significantly reduce LDL-C levels by a maximum of 66% from baseline with a good safety and tolerability profile. Its formulation with sodium caprate enabled a higher bioavailability. Several clinical trials are currently underway to evaluate the efficacy and safety of this drug, including an outcome trial. AZD0780 is another oral small molecule that lowers LDL-C levels by 52% and can be administered on top of a statin. Several other small molecules with the potential to inhibit PCSK9 have been identified, some of which have stopped the development. Oral PCSK9 inhibitors are showing promising results in early studies. If the results of the outcome studies will be positive, we will have a safe, effective and easy-to-use oral therapy. Oral PCSK9 inhibitors could provide a convenient alternative to injectable PCSK9 inhibitors and result in a greater number of patients receiving an effective LDL-C-lowering therapy.
100 项与 Laroprovstat 相关的药物交易
登录后查看更多信息
外链
| KEGG | Wiki | ATC | Drug Bank |
|---|---|---|---|
| D13286 | - | - | - |
研发状态
10 条进展最快的记录, 后查看更多信息
登录
| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 高胆固醇血症 | 临床3期 | - | 2026-09-15 | |
| 杂合子家族性高胆固醇血症 | 临床3期 | 美国 | 2025-06-10 | |
| 杂合子家族性高胆固醇血症 | 临床3期 | 日本 | 2025-06-10 | |
| 杂合子家族性高胆固醇血症 | 临床3期 | 阿根廷 | 2025-06-10 | |
| 杂合子家族性高胆固醇血症 | 临床3期 | 澳大利亚 | 2025-06-10 | |
| 杂合子家族性高胆固醇血症 | 临床3期 | 巴西 | 2025-06-10 | |
| 杂合子家族性高胆固醇血症 | 临床3期 | 保加利亚 | 2025-06-10 | |
| 杂合子家族性高胆固醇血症 | 临床3期 | 加拿大 | 2025-06-10 | |
| 杂合子家族性高胆固醇血症 | 临床3期 | 智利 | 2025-06-10 | |
| 杂合子家族性高胆固醇血症 | 临床3期 | 捷克 | 2025-06-10 |
登录后查看更多信息
临床结果
临床结果
适应症
分期
评价
查看全部结果
临床1期 | 100 | 齋選膚觸築淵築選餘選(餘選鹽遞觸壓壓願壓醖) = 範夢壓觸窪製醖壓顧繭 糧願廠積遞構簾齋膚艱 (築繭鬱鑰顧窪醖築糧鑰, 38 ~ 18) 更多 | 积极 | 2026-06-23 | |||
齋選膚觸築淵築選餘選(餘選鹽遞觸壓壓願壓醖) = 醖鬱齋構鏇鹽齋糧襯鑰 糧願廠積遞構簾齋膚艱 (築繭鬱鑰顧窪醖築糧鑰, 58 ~ 44) 更多 | |||||||
临床2期 | 428 | (AZD0780 1 mg) | 糧製繭鏇衊網鹽觸衊糧(觸餘簾遞醖鹽鏇顧膚壓) = 遞鹽淵遞簾遞夢蓋艱襯 築齋鑰構鹹範範鬱顧淵 (顧衊觸觸糧壓繭糧遞簾, 遞顧蓋餘壓築願夢廠醖 ~ 襯窪築餘窪膚鬱範蓋遞) 更多 | - | 2025-11-17 | ||
(AZD0780 3 mg) | 糧製繭鏇衊網鹽觸衊糧(觸餘簾遞醖鹽鏇顧膚壓) = 鹽衊齋鬱選衊鬱淵鏇簾 築齋鑰構鹹範範鬱顧淵 (顧衊觸觸糧壓繭糧遞簾, 顧獵獵簾鏇製鑰糧壓壓 ~ 獵構窪鏇鹽窪選蓋餘鹽) 更多 | ||||||
临床2期 | 426 | 餘襯網齋選築鹽製積壓(顧夢艱簾觸觸夢鬱憲鹽) = 獵糧廠繭鹹築廠構鹽壓 製築簾簾遞餘簾積襯顧 (艱鹹積築網艱製糧糧積 ) | 积极 | 2025-03-27 | |||
AZD0780 1mg | 淵網選糧齋獵壓鹹鏇製(齋網簾鹽憲廠醖鹽顧觸) = 艱蓋壓鏇壓夢衊獵鑰築 膚獵醖齋選觸選壓壓廠 (糧鏇鬱廠鹽簾夢廠淵鑰 ) | ||||||
临床1期 | - | 選遞鹽鹽鹽鑰繭築艱憲(糧壓製蓋夢衊觸鏇獵構) = None 鹹糧獵蓋願鬱網廠範蓋 (範壓獵襯願繭鬱製積觸 ) | 积极 | 2024-05-29 |
登录后查看更多信息
转化医学
使用我们的转化医学数据加速您的研究。
登录
或
药物交易
使用我们的药物交易数据加速您的研究。
登录
或
核心专利
使用我们的核心专利数据促进您的研究。
登录
或
临床分析
紧跟全球注册中心的最新临床试验。
登录
或
批准
利用最新的监管批准信息加速您的研究。
登录
或
特殊审评
只需点击几下即可了解关键药物信息。
登录
或
提出任何生物医药研究问题
让每一步生物医药决策都精准制胜
基于十亿级生物数据与全球情报的精准 AI，赋能早期药物发现
立即开始免费试用!
智慧芽新药情报库是智慧芽专为生命科学人士构建的基于AI的创新药情报平台，助您全方位提升您的研发与决策效率。
立即接入生物医药数据包
智慧芽新药库数据也通过智慧芽开放平台，以MCP或API服务形式对外开放。立即使用我们的MCP服务定制您的LLM智能体。
生物序列数据库
生物药研发创新
免费使用
化学结构数据库
小分子化药研发创新
免费使用