更新于：2024-11-01

mTOR x NF-κB x APOE x APP

更新于：2024-11-01

基本信息

关联

项与 mTOR x NF-κB x APOE x APP 相关的药物

TML-6

靶点

APOE x APP x NF-κB x mTOR

作用机制

APOE激动剂 [+4]

在研机构

美力龄生医股份有限公司 [+1]

原研机构

美力龄生医股份有限公司

在研适应症

阿尔茨海默症

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

项与 mTOR x NF-κB x APOE x APP 相关的临床试验

NCT06562114 / Recruiting临床1期

A Phase 1, Safety, Tolerability, Single-ascending Dose, Multiple-ascending Dose, Food Effect, and Pharmacokinetic Study of TML-6 in Healthy Volunteers

The purpose of this study is to evaluate the safety, tolerability, single-ascending dose (SAD), multiple-ascending dose (MAD), food effect, and pharmacokinetic (PK) Study of TML-6.

开始日期2024-07-11

申办/合作机构

美力龄生医股份有限公司

100 项与 mTOR x NF-κB x APOE x APP 相关的临床结果

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100 项与 mTOR x NF-κB x APOE x APP 相关的转化医学

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0 项与 mTOR x NF-κB x APOE x APP 相关的专利（医药）

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项与 mTOR x NF-κB x APOE x APP 相关的文献（医药）

International Journal of Molecular Sciences2区 · 生物学

A Curcumin Analog Exhibits Multiple Biologic Effects on the Pathogenesis of Alzheimer’s Disease and Improves Behavior, Inflammation, and β-Amyloid Accumulation in a Mouse Model

2区 · 生物学

ArticleOA

作者: Wang, Hui-Chen ; Su, Ih-Jen ; Tsai, Kuen-Jer ; Chang, Hong-Yi

Drugs for the treatment of Alzheimer’s disease (AD) are in urgent demand due to the unmet need and the social burden associated with the disease. Curcumin has been historically considered as a beneficial product for anti-aging and AD. However, many efforts to develop curcumin for clinical use are hindered mainly due to its poor bioavailability. Recent development in drug delivery and structural design has resolved these issues. In this study, we identified a small molecule, TML-6, as a potential drug candidate for AD through screening a panel of curcumin derivatives using six biomarker platforms related to aging biology and AD pathogenesis. The structural modification of TML-6 is designed to improve the stability and metabolism of curcumin. Cell biological studies demonstrated that TML-6 could inhibit the synthesis of the β-amyloid precursor protein and β-amyloid (Aβ), upregulate Apo E, suppress NF-κB and mTOR, and increase the activity of the anti-oxidative Nrf2 gene. In the 3x-Tg AD animal model, TML-6 treatment resulted in significant improvement in learning, suppression of the microglial activation marker Iba-1, and reduction in Aβ in the brain. Although TML-6 exhibited a greater improvement in bioavailability as compared to curcumin, formulation optimization and toxicological studies are under development to assure its druggability. Taken together, TML-6 meets the current strategy to develop therapeutics for AD, targeting the combination of the Aβ cascade and aging-related biology processes.

项与 mTOR x NF-κB x APOE x APP 相关的新闻（医药）

2024-06-07

·PRNewswire

MLB Announces IND Approval by US FDA to Initiate Phase 1 Trial of TML-6, a New Era Multi-Target Drug for the Treatment of Alzheimer's Disease

TAINAN, June 7, 2024 /PRNewswire/ -- MLB (Merry Life Biomedical Company, Ltd., Taiwan: ), a biomedical company, announced that the U.S. Food and Drug Administration (FDA) has approved IND application for TML-6, an novel drug to treat Alzheimer's disease (AD), enabling a Phase 1 clinical trial to be initiated this July. Advancing TML-6 into clinical trial is a critical milestone for MLB to develop a new era multi-target drug for AD since 2018. About TML-6 Continue Reading TML-6 is a novel synthetic curcumin analog. Professor Ih-Jen Su at Southern Taiwan University used a platform of 6 aging and AD biomarkers to screen the 12 compounds from Androscience (San Diego, USA) for AD candidate. Preclinical studies showed that TML-6 (ASC-6) exhibits a multi-target action mechanism for AD, including anti-aging, activation of autophagy (mTOR inhibitor), reducing amyloid accumulation, and anti-inflammation (Figure 1), the efficacy confirmed by 2 AD animal models. TML-6 has a high bioavailability through formulation and then completed preclinical toxicology and safety studies. TML-6 should be potentially a novel drug to improve or reverse the progression of early-stage AD. The Design and Future Plan of TML-6 for AD Clinical Trial s TML-6 is developed as an oral drug and will conduct a SAD/MAD phase 1 clinical trial at Glendale Adventist Medical Center, LA, USA in 2024 Q3. Elderly cohort and CSF pharmacokinetics (PK) studies were specifically designed. For a global multi-site phase 2a clinical trial, several distinguished global AD experts provided consultation. Blood biomarkers will be included in the phase 2a trial as the surrogate endpoint of efficacy. Furthermore, TML-6 is considering to combine with the current anti-amyloid drugs in phase 2 trial. The drug combination could not only exhibit synergistic effects to improve AD behavior, reducing amyloid accumulation and ant-inflammation, but can also reduce antibody dosing to only 10% and avoid the adverse events (ARIAs) of anti-body drugs. MLB has successfully raised funds to conduct this global phase 2a clinical trial, scheduled to be conducted on 2025 Q3. Contact: Chien Hong Lin, PhD Email: [email protected] SOURCE Merry Life Biomedical Company, Ltd.