AMPK activator

ATX-304, formerly O304, is a pan-AMPK activator from Betagenon developed as a type 2 diabetes drug and exercise mimetic. In a phase IIa trial in people with type 2 diabetes already on metformin, it lowered fasting glucose and insulin resistance and improved microvascular perfusion. In a 2026 phase 1b trial in 23 adults with obesity and prediabetes, 400 mg a day for 8 weeks was reported to lower liver fat, visceral fat and triglycerides and to raise resting metabolic rate, with minimal weight loss; so far that trial exists only as a poster abstract and a company press release. Newer mouse work extends it to fatty liver and kidney injury. The developer's patents describe a milled sodium salt: in volunteers, about a quarter of the dose in enteric capsules matched the blood levels of the original suspension, and rabbit work suggests both the salt and the milled capsule formulation contribute.

J147 is a synthetic small molecule from the Salk Institute. It descends from curcumin through a series of hybrid compounds and was chosen because it protected neurons in six different cell models of brain aging. Fed to mice, it improved memory in normal animals, in Alzheimer's-model mice treated late in the disease and in rapidly aging SAMP8 mice. Its target turned out to be the mitochondrial ATP synthase, which it partly inhibits, switching on AMPK. A phase 1 trial in healthy volunteers finished in 2020 and has never reported results, so there is no published human data at any dose.

MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA, not in the cell nucleus. In mice, injections prevented diet-induced obesity and insulin resistance and improved running capacity at every age tested. In people, exercise raises the body's own MOTS-c, but no trial has given MOTS-c to humans, and measurements of it in blood disagree between methods.