{"_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."},"_self":{"principle":"Self-explaining payload — no external context required. This _self block describes what you are reading and where to look next.","widget":"article_topology","feature":"topology","name":"Article topology","what":"Claims, sources, anecdotes, user reports, related embeds, question graph slice — for ask/ROUTER.","contains":"claims, sources, anecdotes, question_graph slice","slug":"atx-304","urls":{"read":"https://miscsubjects.com/api/articles/atx-304/topology"},"how_to_use":"Claims, sources, anecdotes, user reports, related embeds, question graph slice — for ask/ROUTER.","write":null,"imessage":null,"router_tag":null,"proof_chain":[{"step":1,"claim":"Articles are voxel graphs of tiered claims, not prose blobs.","verify":"https://miscsubjects.com/api/articles/constitution"},{"step":2,"claim":"Claims link to hash-chained sources via source_ids.","verify":"https://miscsubjects.com/api/articles/atx-304/sources"},{"step":3,"claim":"Ask reads topology; ingest/claim append to ledger.","verify":"https://miscsubjects.com/api/protocol"},{"step":4,"claim":"Models queue growth: populate → collaborate → repair → reflex.","verify":"https://miscsubjects.com/api/protocol/grow"},{"step":5,"claim":"Graph proves its own shape (reflex) and $/claim (yield).","verify":"https://miscsubjects.com/graph.html?layer=reflex"},{"step":6,"claim":"Full feature index + _explain on every API response.","verify":"https://miscsubjects.com/api/articles/system-map"}],"related_features":[{"id":"ask","name":"Ask protocol","what":"Answer only from topology; creates question_node with gaps and ingest_hint.","urls":{"read":"https://miscsubjects.com/api/articles/atx-304/prompts","write":"https://miscsubjects.com/api/protocol/ask"}},{"id":"graph_topology","name":"Cross-article graph","what":"Merged claims/sources across condition+stack slugs for one question.","urls":{"read":"https://miscsubjects.com/api/articles/atx-304/graph-topology?question=..."}},{"id":"question_graph","name":"Question graph","what":"Ask nodes (questions + gaps) and evidence_ingest nodes (pasted model output).","urls":{"read":"https://miscsubjects.com/api/articles/atx-304/question-graph","write":"https://miscsubjects.com/api/protocol/ask"}},{"id":"voxels","name":"Voxel graph","what":"Claims as atoms, sources as edges (supported_by, posted_by). Per-claim provenance.","urls":{"read":"https://miscsubjects.com/api/articles/atx-304/voxels","write":"https://miscsubjects.com/api/protocol/claim"}}],"system_map":"https://miscsubjects.com/api/articles/system-map","system_map_markdown":"https://miscsubjects.com/api/articles/system-map?format=markdown","not_medical_advice":true},"_explain":{"feature":"topology","name":"Article topology","what":"Claims, sources, anecdotes, user reports, related embeds, question graph slice — for ask/ROUTER.","why":"Every feature is auditable collective intelligence","how":"Claims, sources, anecdotes, user reports, related embeds, question graph slice — for ask/ROUTER.","model":null,"verifies":null,"urls":{"read":"https://miscsubjects.com/api/articles/atx-304/topology"},"imessage":null,"router":null,"related":[{"id":"ask","what":"Answer only from topology; creates question_node with gaps and ingest_hint."},{"id":"graph_topology","what":"Merged claims/sources across condition+stack slugs for one question."},{"id":"question_graph","what":"Ask nodes (questions + gaps) and evidence_ingest nodes (pasted model output)."},{"id":"voxels","what":"Claims as atoms, sources as edges (supported_by, posted_by). Per-claim provenance."}],"not_medical_advice":true},"slug":"atx-304","title":"ATX-304 activates AMPK directly, and is the only compound in this catalogue tested in patients","register":"canonical","tags":["atx-304","o304","AMPK","type 2 diabetes","MASLD","phase IIa"],"updated_at":"2026-08-05T09:39:21.904Z","body_excerpt":"ATX-304 is the only compound in this part of the catalogue that has been given to patients in a published clinical trial. That single fact separates it from almost everything sold beside it, and it is the reason to read about it differently.\n\nIt also travels under two names, which is the first thing to sort out. The molecule was developed at Umeå University in Sweden by a company called Betagenon and published as **O304**. The name **ATX-304** belongs to Astex and later Cambrian Bio, who licensed it. Same compound, different stage of its life. Search only for ATX-304 and you will miss the human trial, because the human trial was published under O304.\n\n## What AMPK is, and why activating it is a serious idea\n\nEvery cell in your body runs on a molecule called ATP. Using ATP spends it and turns it into ADP and then AMP, so the ratio of AMP to ATP inside a cell is a direct read-out of how depleted that cell is. AMP-activated protein kinase — AMPK — is the protein that reads that ratio. When AMP rises, AMPK switches on, and when AMPK switches on it does two things at once: it turns off the processes that consume energy to build things, and it turns on the processes that release energy by breaking things down.\n\nIn practice that means AMPK activation pulls glucose out of the bloodstream into muscle, tells cells to burn fat rather than store it, stops the liver making new fat and new cholesterol, and increases the number and quality of mitochondria. The paper that introduced O304 describes AMPK as \"a master regulator of energy homeostasis\" that \"is activated in response to an energy shortage imposed by physical activity and caloric restriction.\"\n\nRead that last clause carefully, because it is the whole appeal. Exercise activates AMPK. So does eating less. So, indirectly, does metformin, the most prescribed drug in type 2 diabetes and the one with the best long-term safety record in the entire field. AMPK is not a speculative target — it is the target that the two most reliable metabolic interventions in existence both converge on.\n\nWhich is exactly why it has been so hard to drug directly. Many compounds activate AMPK indirectly by making cells energy-stressed, which works but comes with the consequences of making cells energy-stressed. Activating the kinase directly, without poisoning the cell into doing it, is the harder problem. The 2025 liver paper states the position plainly: \"Despite efforts to target AMPK, no direct activators have yet been approved for treatment of this disease.\"\n\n## The human trial, and exactly what it showed\n\nThe 2018 paper in *JCI Insight* reports both animal and human work. In diet-induced obese mice, O304 \"increased glucose uptake in skeletal muscle, reduced β cell stress, and promoted β cell rest.\" Beta cells are the cells in your pancreas that make insulin; in type 2 diabetes they are working overtime against tissues that have stopped listening, and eventually they fail. Reducing their workload is a different and more interesting goal than pushing them harder, which is what several older diabetes drugs do.\n\nThen the human part, in the paper's own words:\n\n> \"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.\"\n\nThree things in that sentence deserve attention. It was a **phase IIa proof-of-concept** trial, which is a small early study designed to show a signal exists, not to establish that a drug works. The patients were **already on metformin**, so the effect measured was on top of an AMPK-adjacent drug they were already taking. And the endpoints were **fasting glucose and HOMA-IR** — a calculated index of insulin resistance — rather than HbA1c, the standard measure of long-term glucose control that regulators actually require.\n\nThe vascular finding is the one that stands out most, because it appeared in both species: O304 \"improved peripheral","ranking":"safety-first (interaction_risk/limitations), then quote-gated effective_weight","claims":[{"id":"c2","text":"AMPK reads the cell's AMP-to-ATP ratio and is the target that exercise, caloric restriction and metformin all converge on, but no direct activator has been approved.","tier":"mechanistic","interaction_risk":false,"status":"active","source_ids":["s5"],"why_material":"It is why this target is taken seriously rather than speculative, and why activating it directly rather than by inducing energy stress is the hard problem worth solving.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.3,"quote_gated":false},{"id":"c10","text":"ATX-304 is an orally available small molecule designed to be peripherally restricted, because AMPK activation in the hypothalamus increases food intake rather than reducing it.","tier":"mechanistic","interaction_risk":false,"status":"active","source_ids":[],"why_material":"Explains a deliberate design choice: a centrally active AMPK activator would fight itself in an obesity indication. It also marks the compound as a metabolic switch rather than an appetite suppressant, unlike tesofensine or the GLP-1 drugs.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.3,"quote_gated":false},{"id":"c1","text":"ATX-304 and O304 are the same compound: O304 is the Betagenon/Umeå name under which the human trial was published, ATX-304 the name acquired on licensing.","tier":"definition","interaction_risk":false,"status":"active","source_ids":["s1","s4"],"why_material":"Searching one name returns a systematically biased half of the literature — ATX-304 alone misses the phase IIa human trial, which is the single most decision-relevant study that exists on this compound.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.1,"quote_gated":false},{"id":"c3","text":"In a phase IIa proof-of-concept trial in type 2 diabetes patients already taking metformin, O304 reduced fasting plasma glucose and HOMA-IR.","tier":"trial","interaction_risk":false,"status":"active","source_ids":["s1"],"why_material":"This is the only published human efficacy result for the compound. The endpoints were fasting glucose and a calculated insulin-resistance index, not the HbA1c that regulators require, and the effect was measured on top of metformin.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.1,"quote_gated":false},{"id":"c4","text":"O304 improved peripheral microvascular perfusion and reduced blood pressure in both animals and type 2 diabetes patients.","tier":"trial","interaction_risk":false,"status":"active","source_ids":["s2"],"why_material":"Microvascular failure produces the complications that actually disable people with diabetes, and metformin does not meaningfully improve perfusion. This is where a direct activator could differentiate rather than duplicate.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.1,"quote_gated":false},{"id":"c5","text":"O304 improved left ventricular stroke volume in mice without increasing heart weight in either mice or rats.","tier":"animal","interaction_risk":false,"status":"active","source_ids":["s3"],"why_material":"Improving cardiac performance by enlarging the heart is the standard hypertrophy concern with anything that does this. The authors measured mass in two species and reported the negative, which is what a careful paper looks like.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.1,"quote_gated":false},{"id":"c6","text":"In a mouse model of progressive fatty liver disease, ATX-304 reduced body fat, blood cholesterol, liver steatosis and fibrosis, but with pronounced heterogeneity between liver lobes and zones.","tier":"animal","interaction_risk":false,"status":"active","source_ids":["s4"],"why_material":"Fibrosis is what turns a fatty liver into a failing one. The heterogeneity is the part a summary drops, and it matters clinically: a biopsy samples one lobe, so an effect that varies by lobe is one a biopsy may misreport.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.1,"quote_gated":false},{"id":"c7","text":"ATX-304 protected against cisplatin-induced acute kidney injury on three independent measures — serum creatinine, NGAL and histology — with target engagement confirmed by acetyl-CoA carboxylase phosphorylation.","tier":"animal","interaction_risk":false,"status":"active","source_ids":["s6","s7"],"why_material":"Three agreeing readouts plus direct proof the kinase was switched on is a stronger result than any single endpoint, and it comes from an independent group.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.1,"quote_gated":false},{"id":"c8","text":"The 2018 human paper carries a substantial conflict of interest: the senior author is a cofounder and shareholder of Betagenon, and five further authors are employees and shareholders.","tier":"regulatory","interaction_risk":false,"status":"active","source_ids":["s1"],"why_material":"It does not make the trial wrong — almost every early trial of a novel compound is run by people with a stake. It does mean independent replication carries weight it would not otherwise need to, which is why the 2024 and 2025 papers matter.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.1,"quote_gated":false},{"id":"c9","text":"ATX-304 has no regulatory approval anywhere, and no completed peer-reviewed phase 2 obesity trial has been published despite the developer describing phase 2 development.","tier":"regulatory","interaction_risk":false,"status":"active","source_ids":[],"why_material":"The absence of a published phase 2 is information about the state of the evidence, not about the state of the science, and it is the gap between what the compound is claimed to be and what is demonstrated.","retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.1,"quote_gated":false}],"sources":[{"id":"s1","type":"pubmed","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.","claim_ids":[],"hash":"c4837f7adc99eb4e9ac104397c1f1c813b629a8eaba0b85c8e1e0d2e811ac285"},{"id":"s2","type":"pubmed","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.","claim_ids":[],"hash":"22fc0852dfddd1330f5d9e36d2d9f56c3d208e3b52a5b78021f8bdb650301763"},{"id":"s3","type":"pubmed","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.","claim_ids":[],"hash":"5740c6d6d83929b3ae2691d9e108d9a714e625270580822c22264bb14074bbd2"},{"id":"s4","type":"pubmed","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.","claim_ids":[],"hash":"12f20eada55bf2783ca9833ca1c3aef865282ae831a4f3f342795a8155c4fbc2"},{"id":"s5","type":"pubmed","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.","claim_ids":[],"hash":"027bf25ddf1c798d3211e2f6d0c845ca430502bddea0b043d5df2f2bc86e8b1d"},{"id":"s6","type":"pubmed","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.","claim_ids":[],"hash":"741f7aa0dc91f5060cd9321bc642b73039879c9a00bcb5927362e327bde8431a"},{"id":"s7","type":"pubmed","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.","claim_ids":[],"hash":"f0ac7a1b272c2110113cd408a9a75b364e46f048abe2d4956049422d53d4ff61"},{"id":"s8","type":"pubmed","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.","claim_ids":[],"hash":"ded34a56d1e0af36ca792dfc334ec9eae6799cfb1b68ebe575ba26060adc9f5d"}],"anecdotal_sources":[],"scientific_sources":[{"id":"s1","type":"pubmed","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.","claim_ids":[],"hash":"c4837f7adc99eb4e9ac104397c1f1c813b629a8eaba0b85c8e1e0d2e811ac285"},{"id":"s2","type":"pubmed","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.","claim_ids":[],"hash":"22fc0852dfddd1330f5d9e36d2d9f56c3d208e3b52a5b78021f8bdb650301763"},{"id":"s3","type":"pubmed","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.","claim_ids":[],"hash":"5740c6d6d83929b3ae2691d9e108d9a714e625270580822c22264bb14074bbd2"},{"id":"s4","type":"pubmed","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.","claim_ids":[],"hash":"12f20eada55bf2783ca9833ca1c3aef865282ae831a4f3f342795a8155c4fbc2"},{"id":"s5","type":"pubmed","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.","claim_ids":[],"hash":"027bf25ddf1c798d3211e2f6d0c845ca430502bddea0b043d5df2f2bc86e8b1d"},{"id":"s6","type":"pubmed","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.","claim_ids":[],"hash":"741f7aa0dc91f5060cd9321bc642b73039879c9a00bcb5927362e327bde8431a"},{"id":"s7","type":"pubmed","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.","claim_ids":[],"hash":"f0ac7a1b272c2110113cd408a9a75b364e46f048abe2d4956049422d53d4ff61"},{"id":"s8","type":"pubmed","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.","claim_ids":[],"hash":"ded34a56d1e0af36ca792dfc334ec9eae6799cfb1b68ebe575ba26060adc9f5d"}],"user_reports":[],"related_articles":[],"question_graph":{"slug":"atx-304","questions":[],"evidence":[],"edges":[],"counts":{"questions":0,"evidence":0,"edges":0}},"honesty":{"active_claims":10,"retracted_claims":0,"cut_claims":0,"challenges":0,"scrub_events":0,"note":"Retracted/cut claims stay on ledger but are excluded from ask unless ?include_inactive=1"},"counts":{"claims":10,"claims_total":10,"sources":8,"anecdotal":0,"scientific":8,"user_reports":0,"questions":0,"evidence_ingests":0}}