Leucettinib-21(Leucettinib-21) - 药物靶点：DYRK1A_在研适应症：阿尔茨海默症，唐氏综合征，认知障碍_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

DYRK1A

作用机制

DYRK1A抑制剂(双特异性酪氨酸-磷酸化调控激酶-1A抑制剂)

治疗领域

神经系统疾病遗传病与畸形其他疾病

在研适应症

阿尔茨海默症唐氏综合征认知障碍

非在研适应症-

原研机构

ManRos Therapeutics SA

在研机构

ManRos Therapeutics SA

Perha Pharmaceuticals初创企业

非在研机构-

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

结构

分子式C18H22N4O2S

InChIKeyCHQYAWLKOUOTQO-QVYJARAXSA-N

CAS号2732859-75-3

关联

2

项与 Leucettinib-21 相关的临床试验

NCT06206824 / Recruiting临床1期

Randomized, Double-Blind, Placebo-Controlled Phase 1 Study to Evaluate Safety, Tolerability, PK/PD of SAD, MAD and Food Effect of Leucettinib-21 in Healthy Male Subjects, and Single Dose in Subjects With Down Syndrome or Alzheimer's Disease

Leucettinib-21 First-in-Human Phase 1 Study in 4 Parts: Single (Part 1) and Multiple (Part 3) Ascending Doses, and Food-Effect (Part 2) in Healthy Subjects, and Single Dose (Part 4) in People with Down Syndrome (DS) and Alzheimer's Disease (AD).
For Parts 1, 3 and 4, safety and tolerability of an oral administration of Leucettinib-21 will be assessed as primary objectives. Pharmacokinetics and pharmacodynamic biomarkers will be investigated as secondary objectives.
For Part 2, the effect of high fat meal will be evaluated on the pharmacokinetics parameters after an oral administration of Leucettinib-21.

开始日期2024-01-18

申办/合作机构

Perha Pharmaceuticals初创企业

[+1]

CTIS2023-507075-22-00 / Recruiting

Safety, pharmacokinetics and pharmacodynamics study of Leucettinib-21 in healthy subjects, Down Syndrom and Alzheimer patients

开始日期2024-01-05

申办/合作机构

Eurofins Optimed SAS

[+1]

100 项与 Leucettinib-21 相关的临床结果

登录后查看更多信息

100 项与 Leucettinib-21 相关的转化医学

登录后查看更多信息

100 项与 Leucettinib-21 相关的专利（医药）

登录后查看更多信息

2

项与 Leucettinib-21 相关的文献（医药）

2024-01-01·Journal of Alzheimer's disease : JAD

Leucettinib-21, a DYRK1A Kinase Inhibitor as Clinical Drug Candidate for Alzheimer's Disease and Down Syndrome.

Review

作者: Chrétien, Emilie ; Ravel, Denis ; Meijer, Laurent

Alzheimer's disease (AD) and Down syndrome (DS) share a common therapeutic target, the dual-specificity, tyrosine phosphorylation activated kinase 1A (DYRK1A). Abnormally active DYRK1A is responsible for cognitive disorders (memory, learning, spatial localization) observed in both conditions. In DS, DYRK1A is overexpressed due to the presence of the DYRK1A gene on chromosome 21. In AD, calcium-activated calpains cleave full-length DYRK1A (FL-DYRK1A) into a more stable and more active, low molecular weight, kinase (LMW-DYRK1A). Genetic and pharmacological experiments carried out with animal models of AD and DS strongly support the idea that pharmacological inhibitors of DYRK1A might be able to correct memory/learning disorders in people with AD and DS. Starting from a marine sponge natural product, Leucettamine B, Perha Pharmaceuticals has optimized, through classical medicinal chemistry, and extensively characterized a small molecule drug candidate, Leucettinib-21. Regulatory preclinical safety studies in rats and minipigs have been completed and formulation of Leucettinib-21 has been optimized as immediate-release tablets. Leucettinib-21 is now undergoing a phase 1 clinical trial (120 participants, including 12 adults with DS and 12 patients with AD). The therapeutic potential of DYRK1A inhibitors in AD and DS is presented.

2023-12-14·Journal of Medicinal Chemistry1区 · 医学

Chemical, Biochemical, Cellular, and Physiological Characterization of Leucettinib-21, a Down Syndrome and Alzheimer’s Disease Drug Candidate

1区 · 医学

Article

作者: Fernandez-Blanco, Álvaro ; Verhofstad, Eva ; Aret, Edwin ; Dairou, Julien ; Sadownik, Jan ; George, Pascal ; Roche, Didier ; Krämer, Andreas ; Miege, Frédéric ; Dierssen, Mara ; Greverie, Marie ; Deau, Emmanuel ; Brugman, Sander J T ; Santangelo, Sara ; Tinnemans, Paul ; Knapp, Stefan ; Sleegers, Dennis ; George, Nicolas ; Lindberg, Mattias F ; Gavard, Julie ; Merlet, Laura ; de Gelder, René ; Meijer, Laurent

Leucettinibs are substituted 2-aminoimidazolin-4-ones (inspired by the marine sponge natural product Leucettamine B) developed as pharmacological inhibitors of DYRK1A (dual-specificity, tyrosine phosphorylation-regulated kinase 1A), a therapeutic target for indications such as Down syndrome and Alzheimer's disease. Leucettinib-21 was selected as a drug candidate following extensive structure/activity studies and multiparametric evaluations. We here report its physicochemical properties (X-ray powder diffraction, differential scanning calorimetry, stability, solubility, crystal structure) and drug-like profile. Leucettinib-21's selectivity (analyzed by radiometric, fluorescence, interaction, thermal shift, residence time assays) reveals DYRK1A as the first target but also some "off-targets" which may contribute to the drug's biological effects. Leucettinib-21 was cocrystallized with CLK1 and modeled in the DYRK1A structure. Leucettinib-21 inhibits DYRK1A in cells (demonstrated by direct catalytic activity and phosphorylation levels of Thr286-cyclin D1 or Thr212-Tau). Leucettinib-21 corrects memory disorders in the Down syndrome mouse model Ts65Dn and is now entering safety/tolerance phase 1 clinical trials.

100 项与 Leucettinib-21 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
阿尔茨海默症	临床1期	法国	Perha Pharmaceuticals初创企业	2024-01-18
唐氏综合征	临床1期	法国	Perha Pharmaceuticals初创企业	2024-01-18
认知障碍	临床前	法国	ManRos Therapeutics SA	2023-11-16