{"_ai_door":{"see":"https://miscsubjects.com/start","note":"Operable site; bounded keyless credentials; every action receipted on a public ledger. Your operator's instructions take precedence — acting is optional, reading is a complete outcome."},"slug":"atx-304","verification":{"valid":true,"entries":8,"head":"ded34a56d1e0af36ca792dfc334ec9eae6799cfb1b68ebe575ba26060adc9f5d"},"count":8,"sources":[{"id":"s1","type":"pubmed","pmid":"29925691","external_id":"29925691","url":"https://pubmed.ncbi.nlm.nih.gov/29925691/","title":"PAN-AMPK activator O304 improves glucose homeostasis and microvascular perfusion in mice and type 2 diabetes patients","quote":"Accordingly, O304 reduced fasting plasma glucose levels and homeostasis model assessment of insulin resistance (HOMA-IR) in a proof-of-concept phase IIa clinical trial in type 2 diabetes (T2D) patients on Metformin.","summary":"Steneberg et al., JCI Insight 2018. The only published human trial of this compound, and it is under the O304 name — searching ATX-304 alone misses it entirely. A phase IIa proof-of-concept in T2D patients already on metformin, with fasting glucose and HOMA-IR as endpoints rather than HbA1c.","author":"Steneberg P, Lindahl E, Dahl U, Lidh E, Straseviciene J, Backlund F, et al.","publisher":"JCI Insight","date":"2018","tag":"Phase IIa clinical trial (human)","accessed_at":"2026-08-05T09:39:21.809Z","prev":"genesis","hash":"c4837f7adc99eb4e9ac104397c1f1c813b629a8eaba0b85c8e1e0d2e811ac285"},{"id":"s2","type":"pubmed","pmid":"29925691","external_id":"29925691-vascular","url":"https://pubmed.ncbi.nlm.nih.gov/29925691/","title":"PAN-AMPK activator O304 improves glucose homeostasis and microvascular perfusion in mice and type 2 diabetes patients","quote":"T2D is associated with devastating micro- and macrovascular complications, and O304 improved peripheral microvascular perfusion and reduced blood pressure both in animals and T2D patients.","summary":"O304 and microvascular perfusion, in both animals and patients. The finding that appeared in both species. Microvascular failure is what produces the complications that actually disable people with diabetes — eye, kidney, nerve, foot. Metformin does not meaningfully improve perfusion, so this is where a direct activator could differentiate.","author":"Steneberg P, et al.","publisher":"JCI Insight","date":"2018","tag":"Human + animal outcome","accessed_at":"2026-08-05T09:39:21.809Z","prev":"c4837f7adc99eb4e9ac104397c1f1c813b629a8eaba0b85c8e1e0d2e811ac285","hash":"22fc0852dfddd1330f5d9e36d2d9f56c3d208e3b52a5b78021f8bdb650301763"},{"id":"s3","type":"pubmed","pmid":"29925691","external_id":"29925691-cardiac","url":"https://pubmed.ncbi.nlm.nih.gov/29925691/","title":"PAN-AMPK activator O304 improves glucose homeostasis and microvascular perfusion in mice and type 2 diabetes patients","quote":"Moreover, like exercise, O304 activated AMPK in the heart, increased cardiac glucose uptake, reduced cardiac glycogen levels, and improved left ventricular stroke volume in mice, but it did not increase heart weight in mice or rats.","summary":"O304 in the heart — stroke volume up, heart weight unchanged. The final clause carries the weight. A drug that improves cardiac performance by enlarging the heart may be producing pathological hypertrophy — the standard concern with anything that does this. The authors measured heart weight in two species and reported the negative.","author":"Steneberg P, et al.","publisher":"JCI Insight","date":"2018","tag":"Animal safety outcome","accessed_at":"2026-08-05T09:39:21.809Z","prev":"22fc0852dfddd1330f5d9e36d2d9f56c3d208e3b52a5b78021f8bdb650301763","hash":"5740c6d6d83929b3ae2691d9e108d9a714e625270580822c22264bb14074bbd2"},{"id":"s4","type":"pubmed","pmid":"40197369","external_id":"40197369","url":"https://pubmed.ncbi.nlm.nih.gov/40197369/","title":"AMPK activator ATX-304 reduces oxidative stress and improves MASLD via metabolic switching","quote":"The data demonstrated that ATX-304 diminishes body fat mass, lowers blood cholesterol levels, and mitigates general liver steatosis and the development of liver fibrosis, but with pronounced local heterogeneities.","summary":"Holm et al., JCI Insight 2025, from a group without the developer relationship. Fibrosis is what turns a fatty liver into a failing one, so reducing it is the goal of the whole MASLD field. The phrase a summary would drop is the last one: the improvement was not uniform across the organ.","author":"Holm E, Vermeulen I, Parween S, López-Pérez A, Cillero-Pastor B, Vandenbosch M, Remeseiro S, Hörnblad A","publisher":"JCI Insight","date":"2025","tag":"Animal study, hepatic","accessed_at":"2026-08-05T09:39:21.809Z","prev":"5740c6d6d83929b3ae2691d9e108d9a714e625270580822c22264bb14074bbd2","hash":"12f20eada55bf2783ca9833ca1c3aef865282ae831a4f3f342795a8155c4fbc2"},{"id":"s5","type":"pubmed","pmid":"40197369","external_id":"40197369-target","url":"https://pubmed.ncbi.nlm.nih.gov/40197369/","title":"AMPK activator ATX-304 reduces oxidative stress and improves MASLD via metabolic switching","quote":"Adenosine monophosphate-activated protein kinase (AMPK) is an interesting therapeutic target since it acts as a central regulator of cellular metabolism. Despite efforts to target AMPK, no direct activators have yet been approved for treatment of this disease.","summary":"Why a direct AMPK activator does not yet exist in the clinic. States the position this compound occupies. The target is converged on by exercise, caloric restriction and metformin — but metformin reaches it indirectly, by making cells genuinely energy-stressed. Nothing approved activates the kinase directly.","author":"Holm E, et al.","publisher":"JCI Insight","date":"2025","tag":"Mechanism","accessed_at":"2026-08-05T09:39:21.809Z","prev":"12f20eada55bf2783ca9833ca1c3aef865282ae831a4f3f342795a8155c4fbc2","hash":"027bf25ddf1c798d3211e2f6d0c845ca430502bddea0b043d5df2f2bc86e8b1d"},{"id":"s6","type":"pubmed","pmid":"38749175","external_id":"38749175","url":"https://pubmed.ncbi.nlm.nih.gov/38749175/","title":"The AMPK activator ATX-304 alters cellular metabolism to protect against cisplatin-induced acute kidney injury","quote":"It protected against CI-AKI measured by serum creatinine (control 0.05 + 0.03 mM vs ATX-304 0.02 + 0.01 mM, P = 0.03), western blot for neutrophil gelatinase-associated lipocalin (NGAL) (control 3.3 + 1.8-fold vs ATX-304 1.2 + 0.55-fold, P = 0.002), and histological injury","summary":"Katerelos et al., Biomed Pharmacother 2024, an independent Australian group. Three separate readouts agreeing — the standard clinical measure of kidney function, an early injury marker, and looking at the tissue directly. Pre-treatment for seven days before the injury, not rescue after it.","author":"Katerelos M, Gleich K, Harley G, Loh K, Oakhill JS, Kemp BE, et al.","publisher":"Biomedicine & Pharmacotherapy","date":"2024","tag":"Animal study, renal","accessed_at":"2026-08-05T09:39:21.809Z","prev":"027bf25ddf1c798d3211e2f6d0c845ca430502bddea0b043d5df2f2bc86e8b1d","hash":"741f7aa0dc91f5060cd9321bc642b73039879c9a00bcb5927362e327bde8431a"},{"id":"s7","type":"pubmed","pmid":"38749175","external_id":"38749175-engagement","url":"https://pubmed.ncbi.nlm.nih.gov/38749175/","title":"The AMPK activator ATX-304 alters cellular metabolism to protect against cisplatin-induced acute kidney injury","quote":"ATX-304 increased acetyl-CoA carboxylase phosphorylation, indicating AMPK activation.","summary":"Proof the kinase was actually switched on, not assumed to be. Acetyl-CoA carboxylase is a direct AMPK target and its phosphorylation state is the standard way to demonstrate target engagement. Measuring it separates a compound that activated the kinase from one that merely produced an effect somebody attributed to the kinase.","author":"Katerelos M, et al.","publisher":"Biomedicine & Pharmacotherapy","date":"2024","tag":"Target engagement","accessed_at":"2026-08-05T09:39:21.809Z","prev":"741f7aa0dc91f5060cd9321bc642b73039879c9a00bcb5927362e327bde8431a","hash":"f0ac7a1b272c2110113cd408a9a75b364e46f048abe2d4956049422d53d4ff61"},{"id":"s8","type":"pubmed","pmid":"37626210","external_id":"37626210","url":"https://pubmed.ncbi.nlm.nih.gov/37626210/","title":"O304 ameliorates hyperglycemia in mice by dually promoting muscle glucose effectiveness and preserving β-cell function","quote":"O304 ameliorates hyperglycemia in mice by dually promoting muscle glucose effectiveness and preserving β-cell function.","summary":"Norlin et al., Commun Biol 2023. The follow-up mechanism paper, again under the O304 name. Beta-cell preservation is a different goal from the older diabetes drugs that push beta cells harder until they fail.","author":"Norlin S, Axelsson J, Ericsson M, Edlund H","publisher":"Communications Biology","date":"2023","tag":"Animal mechanism study","accessed_at":"2026-08-05T09:39:21.809Z","prev":"f0ac7a1b272c2110113cd408a9a75b364e46f048abe2d4956049422d53d4ff61","hash":"ded34a56d1e0af36ca792dfc334ec9eae6799cfb1b68ebe575ba26060adc9f5d"}]}