预约演示
更新于：2026-05-25
DNL-151
更新于：2026-05-25
概要
基本信息
原研机构 |
非在研机构- |
最高研发阶段临床2期 |
首次获批日期- |
最高研发阶段(中国)临床2期 |
特殊审评- |
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关联
9
项与 DNL-151 相关的临床试验NCT06602193
A Phase 2a, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Pharmacodynamic Effects of BIIB122 in Participants With LRRK2-Associated Parkinson's Disease (LRRK2-PD)
NCT06264440
A Phase 1, Open-Label, Crossover Study to Assess the Potential for Gastric pH-Dependent Drug-Drug Interactions of BIIB122 With a Proton Pump Inhibitor in Healthy Participants
NCT05418673
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of BIIB122/DNL151 in Participants With Parkinson's Disease and Pathogenic LRRK2 Variants
100 项与 DNL-151 相关的临床结果
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100 项与 DNL-151 相关的转化医学
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100 项与 DNL-151 相关的专利（医药）
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3
项与 DNL-151 相关的文献（医药）2023-12-01Bioorganic chemistry
Recent advances in targeting leucine-rich repeat kinase 2 as a potential strategy for the treatment of Parkinson’s disease
Review
作者: Longhui Sun ; Weihe Zhao ; Liyan Yuan ; Lei Shan ; Chunlei Wu ; Caiping Chen ; Chaojun Zhang ; Haopeng Sun ; Jing Wen ; Meiyang Xi ; Ruiwei Cao
Parkinson's disease (PD) is the second most common neurodegenerative disease. Several single gene mutations involved in PD have been identified such as leucine-rich repeat kinase 2 (LRRK2), the most common cause of sporadic and familial PD. Its mutations have attracted much attention to therapeutically targeting this kinase. To date, many compounds including small chemical molecules with diverse scaffolds and RNA agents have been developed with significant amelioration in preclinical PD models. Currently, five candidates, DNL201, DNL151, WXWH0226, NEU-723 and BIIB094, have advanced to clinical trials for PD treatment. In this review, we describe the structure, pathogenic mutations and the mechanism of LRRK2, and summarize the development of LRRK2 inhibitors in preclinical and clinical studies, trying to provide an insight into targeting LRRK2 for PD intervention in future.
2023-09-02Expert opinion on investigational drugs
DNL151, DNL201, and BIIB094: experimental agents for the treatment of Parkinson’s disease
Review
作者: Müller, Thomas
INTRODUCTION:
Pathogenic mutations of the abundant leucine-rich repeat kinase 2 gene support the onset of familial and sporadic forms of Parkinson's disease. These genetic variants catalyze kinase activity by substrate phosphorylation. They promote the nigrostriatal neurodegenerative process, i.e. characterized by Lewy body formation.
AREAS COVERED:
This narrative review discusses leucine-rich repeat kinase 2 inhibitors as therapeutic concept for beneficial disease modification following a literature search.
EXPERT OPINION:
Leucine-rich repeat kinase 2 gene function contributes to the onset of microglia inflammation, cellular, and mitochondrial dysfunction. Leucine-rich repeat kinase 2 inhibition with oral application of DNL151, respectively DNL201, and intrathecal administration of the antisense oligonucleotide BIIB094 in a single and multiple ascending dose study was safe and well tolerated. Approval of Leucine-rich repeat kinase 2 inhibitors in case of positive clinical study outcomes will introduce personalized medicine for beneficial modification of progression as the most unmet need for treatment of patients with Parkinson's disease. In addition to the currently, preponderantly performed clinical rating with established scales, further clinical trial endpoints, such as dosing of dopamine substitution, may be considered in study designs to demonstrate therapeutic effects on the progression of Parkinson's disease.
2020-04-02Expert opinion on therapeutic patents2区 · 医学
Leucine-rich repeat kinase 2 inhibitors: a patent review (2014-present)
2区 · 医学
Review
作者: Ren, Feng ; Ding, Xiao
Introduction: Disease-modifying treatment for Parkinson's disease (PD) to halt or revert the disease progression remains an unmet medical need. LRRK2 kinase activity is abnormally elevated in PD patients carrying LRRK2 mutations, with G2019S as the most frequent one. Small molecules to inhibit LRRK2 kinase activity might provide a potential disease-modifying strategy for PD.Areas covered: This review provides an update of small molecule LRRK2 inhibitors in patents published from January 2014 to October 2019. The molecules are classified by their structural scaffolds.Expert opinion: Despite the tremendous efforts to push small molecule LRRK2 inhibitors toward clinical trials, the overall progress is somewhat disappointing due to the challenges in compound optimization and the putative concern of target-related adverse effects. It is challenging to optimize multiple parameters including kinase selectivity, CNS penetration, and unbound fraction in brain simultaneously. In addition, the on-target effect of morphologic changes observed in lung/kidney in pre-clinical studies for several frontrunner ATP-competitive inhibitors prevented their further development. With this regard, non-ATP-competitive inhibitors may provide a different safety profile for development. DNL201 and DNL151 have entered early clinical trials to evaluate tolerability and target engagement biomarkers. This will pave the way for the development for future LRRK2 inhibitors.
100 项与 DNL-151 相关的药物交易
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研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 帕金森病 | 临床3期 | 美国 | 2022-08-26 | |
| 帕金森病 | 临床3期 | 美国 | 2022-08-26 | |
| 帕金森病 | 临床3期 | 法国 | 2022-08-26 | |
| 帕金森病 | 临床3期 | 法国 | 2022-08-26 | |
| 帕金森病 | 临床3期 | 德国 | 2022-08-26 | |
| 帕金森病 | 临床3期 | 德国 | 2022-08-26 | |
| 帕金森病 | 临床3期 | 意大利 | 2022-08-26 | |
| 帕金森病 | 临床3期 | 意大利 | 2022-08-26 | |
| 帕金森病 | 临床3期 | 西班牙 | 2022-08-26 | |
| 帕金森病 | 临床3期 | 西班牙 | 2022-08-26 |
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临床结果
临床结果
适应症
分期
评价
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临床3期 | 7 | 艱鹽範蓋艱網窪蓋醖選 = 顧餘窪醖醖齋遞築憲衊 齋顧顧衊鹽鹽簾網積觸 (構糧鑰壓膚夢獵襯選餘, 襯憲築醖簾積遞餘壓獵 ~ 廠夢願願鹽齋鏇窪顧鹹) 更多 | - | 2024-06-26 | |||
MDS2023 人工标引  | N/A | 222 | (healthy volunteers and Parkinson’s Participants) | 觸網鑰鏇膚獵鹹簾蓋網(廠餘顧觸積築鑰淵觸遞) = Reduction of urine BMP corresponded to ~80-90% of LRRK2 inhibition based on average concentrations. 願範蓋鑰選獵簾艱願糧 (鏇淵襯壓觸構網鏇憲簾 ) 更多 | 积极 | 2023-08-27 |
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