What If Metabolism Didn’t Have to Drop? (Cambrian)

A new drug candidate that Cambrian is working on…

What if, instead of scrambling to lose weight, we could maintain a healthy metabolism and prevent weight gain as we age? How might a preventive medicine that aids Americans in staying healthier and more active as they grow older transform our families, communities, and economy?

These are the questions our VP of Policy, Adrienne Hallett, poses in her latest instillment of ‘An Ounce of Longevity. In it she explores the vast potential impact of ATX-304, a drug being developed by our PipeCo Amplifier Therapeutics.

ATX-304, which was dosed in the first patients in Amplifier’s Phase 1b clinical trial last month, is a peripherally restricted pan-AMPK activator with the potential to aid in weightloss and maybe even improve cardiac health by increasing metabolism.

https://www.cambrianbio.com/blogs/what-if-metabolism-didnt-have-to-drop

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Yes! This is such a better direction to go in. Been waiting for something like this to show up.

Some diets and some vitamins claim to support AMPK but, unlike those products, this investigational drug is entering the most rigorous of human trials under the direction of expert scientists at Amplifier Therapeutics.

Which is a good marketing phrase.

I agree that AMPK is a good target and this substance ATX-304 may be something that is helpful in terms of tarketing AMPK. It may be, however, that some of the current molecules that target AMPK are worth taking.

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Please, can you give some examples that you think are worthwhile?

Most of the TCM Yang Qi herbs such as ginseng seem to be AMPK activators.

Eg: Astragalus, rhodia, ginko, saffron, gotu kola, schisandra, ginseng , jiaogulan, karelia, cordyceps and daodi/codonopsis,

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Two of the most widely used medicines in the world, metformin, the mostly commonly used drug for type 2 diabetes, and salicylate , the active ingredient in aspirin and salsalate, also activate AMPK, suggesting that some of their beneficial effects may be mediated in part by AMPK

AMP-activated protein kinase: the current landscape for drug development

Nature Reviews Drug Discovery

https://www.nature.com/articles/s41573-019-0019-2#

And… more good news. Drugs that activate AMPK also seem to directly increase mTORC2 (another good thing for longevity).

AMPK directly activates mTORC2 to promote cell survival during acute energetic stress

https://www.science.org/doi/full/10.1126/scisignal.aav3249

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Good find.

We just have to also take into account that end of it’s abstract says

These results may help to explain why AMPK, which is typically thought of as a tumor suppressor, can act as promoter of tumor growth in some contexts.

Also worth taking a look at the part on AMPK / Meformin combined with rapa here (to help avoid rebound)

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