Dual receptor beta-agonist promotes healthy weight loss

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A new research paper has validated the mechanism of action of the Atrogi’s first-in-class, small molecule, ATR-127, in combating obesity and metabolic complications.

Unlike existing anti-obesity therapies that compromise lean muscle mass, ATR-127 induces significant weight loss while preserving crucial lean body mass.

ATR-127 binds to both the beta-2 and beta-3 adrenergic receptors in a unique manner, allowing for precise modulation of downstream signalling cascades.

Its binding mechanism enables selective activation of specific signalling pathways. This unlocks the full therapeutic potential of beta-2 and beta-3 receptor agonism, maximising beneficial effects on metabolism and body composition while mitigating the cardiovascular side effects commonly associated with indiscriminate receptor activation.

Atrogi’s CEO, Alexandra Ekman Ryding, said: “This publication highlights strong pre-clinical data relating to ATR-127 and validates our approach for the development of a novel modality for the treatment of obesity. We are now advancing our next generation small molecules for the treatment of obesity to IND preparatory studies in H1 next year and expect to enter the clinic in 2026.”

Atrogi is also conducting trials into ATR-258, a novel b2adrenoceptor agonist for the treatment of type 2 diabetes and comorbidities. 

Decreasing fat while preserving muscle

The preclinical study found that ATR-127 enhances energy expenditure and promotes beneficial metabolic changes by inducing skeletal muscle glucose uptake and the concomitant activation of brown and beige adipose tissue. This results in healthy weight loss – decreasing fat mass but preserving muscle, whilst reducing hepatic inflammation and lipid content. ATR-127’s ability to deliver precise signalling modulation prevents excessive cAMP production thereby lowering cardiac force production and mitigating risks of cardiovascular side effects.

Atrog’s Founder and CSO, Tore Bengtsson, a Professor of Physiology at Stockholm University, added: “There is a high demand for novel treatments of obesity without the current debilitating side effects and muscle loss. We believe our pioneering dual receptor beta-agonist approach has the potential to transform the obesity treatment landscape. Our vision is for a more holistic treatment for diabesity and steatohepatitis that not only treats the underlying cause of disease but also supports overall health and quality of life.”

This study was a collaborative international effort involving Atrogi  and various academic institutions in Europe and Australia.

Diana Spencer, Senior Digital Content Editor, DDW

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