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TDMQ20, a small molecule as drug-candidate for the treatment of Alzheimer’s disease

Date 30 Jun 2023
Time 4:00 - 5:00 PM
Venue CYC P1
Speaker Prof. Bernard Meunier
Institution Emeritus Researcher of the CNRS, Toulouse, France
Distinguished Professor at the Guangdong University of Technology, Guangzhou
Former President of the French Academy of Sciences

Self Photos / Files - TDMQ20

 

Title:

TDMQ20, a small molecule as drug-candidate for the treatment of Alzheimer’s disease

 

Schedule:

Date: 30 June 2023 (Friday)

Time: Start from 4:00 pm (HKT)

Venue: Lecture Theatre P1, CYM Chemistry Building

 

Abstract: 

Alzheimer’s disease is the major neurodegenerative disease without efficient drugs to stop the evolution of the pathology. Considering that the rupture of metal homeostasis in the brain of AD patients is at the origin of the redox stress that reduces the neuron population, we designed new tetradentate ligands named “TDMQ”.

 

The selected drug-candidate TDMQ20 is able to reverse the cognitive and behavioral impairment in three different murine models, two non-transgenic models mimicking the early stage of AD, and a transgenic representing a more advanced stage of AD.

Proteomic studies performed on transgenic mice treated orally with TDMQ20 clearly evidenced that this drug-candidate is able to (i) reduce the amyloid plaque loading in the cortex, (ii) to restore the cholinergic system and the synaptic transmission and (iii) to enhance the PI3K/Akt signaling pathway (its reduction in AD favors the hyperphosphorylation of tau).4

 

The high bioavailability of TDMQ20 and its capacity to easily penetrate brain has been evidenced in rat when treated orally.5

 

References

  1. Preparation of new tetradentate copper chelators as potential anti-Alzheimer agents.

         Weixin ZHANG, Daya HUANG, Meijie HUANG, Ju HUANG, Dean WANG, Xingguo LIU, Michel NGUYEN, Laure VENDIER, Serge MAZÈRES, Anne ROBERT, Yan LIU, Bernard MEUNIER.

                ChemMedChem., 13, 684-704 (2018).

 

  1. Metal ions in Alzheimers' disease: a key role or not?

         Yan LIU, Michel NGUYEN, Anne ROBERT, Bernard MEUNIER

                Acc. Chem. Res., 52, 2026-2035 (2019).

 

  1. TDMQ20, a specific copper chelator, reduces memory impairments in AD mouse models.

         Zhiao JIE, Qihui SHI, Hongda TIAN, Youzhi LI, Yan LIU, Zhen XU, Anne ROBERT, Quiong LIU, Bernard MEUNIER

                ACS Chem. Neurosc., 12, 140-149 (2021).

 

  1. Proteomics evidences of the role of TDMQ20 in the cholinergic system and synaptic transmission in a mouse model of Alzheimer’s disease.

         Fanfan SUN, Jie ZHIAO, Huajie ZHANG, Qihui SHI, Yan LIU, Anne ROBERT, Qiong LIU, Bernard MEUNIER.

                ACS Chem. Neurosci. 13, 3093-3107 (2022).       

 

  1. Distribution in rat blood and brain of TDMQ20, a copper chelator designed as drug-candidate for Alzheimer’s disease.

         Lan HUANG, Yaoxun ZENG, Yongliang LI, Yinshan ZHU, Yan HE, Yan LIU, Anne ROBERT, Bernard MEUNIER

                Pharmaceutics, 14, 2691(2022).

 

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