Fosgonimeton CAS 2093305-05-4

ATH-1017 Introduction

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Fosgonimeton (ATH-1017) is a small molecule innovative compound developed by Athira Pharma. Its core mechanism of action lies in positively regulating the liver cell growth factor (HGF)/MET signaling pathway. By activating the neurotrophic, neuroprotective and anti-inflammatory pathways within the central nervous system, it aims to address the complex pathological processes of neurodegenerative diseases. In preclinical studies, Fosgonimeton demonstrated the potential to counteract neuronal damage and autophagy dysfunction induced by β-amyloid protein (Aβ), and was associated with improved cognitive function. Currently, Fosgonimeton (ATH-1017) has entered the clinical trial stage, and is mainly being developed for the treatment of Alzheimer's disease (AD). Safety data related to other indications such as Parkinson's disease dementia and Lewy body dementia have also been disclosed in exploratory studies.
Its CAS number: 2093305-05-4; Molecular formula: C27H45N4O8P; Molecular weight: 584.65

How does ATH-1017 exert its effect at the cellular level?

It can be regarded as a kind of "signal enhancer". Fosgonimeton does not directly alter the neurons themselves, but acts on the receptor complexes on the cell surface, making the nerve cells more sensitive to the "survival signals" in the surrounding environment - hepatocyte growth factor. Once the signal is amplified, multiple protective pathways within the cells will be activated, including inhibiting the release of inflammatory factors, maintaining the energy supply of mitochondria, and initiating the recycling mechanism of damaged proteins. This is equivalent to providing an additional layer of protection for the neurons in a stressed state.

Apart from Alzheimer's disease, what other diseases has ATH-1017 been explored for?

Researchers have expanded the application scope of Fosgonimeton to other brain diseases characterized by abnormal protein deposition. For instance, in preclinical models of Parkinson's disease dementia and Lewy body dementia, ATH-1017 was observed to alleviate the synaptic dysfunction caused by α-synuclein. Additionally, there have been sporadic exploratory studies focusing on its role in the chronic inflammatory stage following traumatic brain injury, but most of these directions have remained at the early proof-of-concept stage and have not entered large-scale clinical trials.

MF of Fosgonimeton(ATH-1017)

CAS	2093305-05-4
Molecular formula	C27H45N4O8P
Molecular weight	584.65
Form	Solid
Acidity coefficient	1.27±0.30
Density	1.212±0.06 g/cm3

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FAQ: 

Q1:What is the safety profile of ATH-1017?
The overall safety was considered acceptable, and the occurrence of serious adverse events was balanced between the two groups. However, there was a notable situation: the dropout rate in the ATH-1017 group (14.2%) was significantly higher than that in the placebo group (4.6%), and the main reason for dropout was adverse reactions related to the use of this compound.
Q2:How did ATH-1017 perform in animal experiments?

It shows positive results in multiple animal models. For instance, it can reverse the memory impairment caused by Scopolamine, improve the signal disorder of Choline hydroxide; and also counteract the cognitive impairment caused by neuroinflammation induced by lipopolysaccharide (LPS). These results provide certain basis for its entry into human clinical trials.

Q3:Can it pass through the blood-brain barrier?

This is precisely one of the purposes of the design of its predecessor product. The ATH-1017 itself has better solubility and stability, and can more effectively enter the central nervous system through the bloodstream. After entering the brain, it then transforms into an active metabolite, which then functions on the nerve cells at the target location - that is, within the brain tissue.

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