ATX-304 / Cambrian Biopharma - LARVOL DELTA

Weight Loss and Change in Body Composition in a DIO Mouse Model by the Combined AMPK and Mitochondrial Activator, ATX-304, Alone, in Combination With Semaglutide, and After Semaglutide Withdrawal (ENDO 2025) - "Based on results from this mouse model, ATX is a promising new weight loss agent with complementary effects to incretins, including preservation of lean mass. ATX may be useful as monotherapy, in coadministration, or as weight maintenance therapy in patients discontinuing incretins.*. .*"

Combination therapy • Preclinical • Cardiovascular • Genetic Disorders • Metabolic Disorders • Obesity • AMPK

AMPK activator ATX-304 reduces oxidative stress and improves MASLD via metabolic switching. (PubMed, JCI Insight) - "We also observed variations in lipid distribution among liver lobes in response to ATX-304, and a shift in the zonal distribution of lipid droplets upon treatment. Taken together, our data suggested that ATX-304 holds promise as a potential treatment for MASLD."

Journal • Fibrosis • Gastroenterology • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

O304 alleviates abdominal aortic aneurysm formation via AMPK/mTOR/MMP pathway activation. (PubMed, Front Pharmacol) - "O304, an AMPK agonist, activated the AMPK pathway, preventing VSMC phenotypic switching and inhibiting AAA formation. These findings highlight the therapeutic potential of targeting the AMPK pathway in AAA."

Journal • Cardiovascular • TGFB1

NTRK1 knockdown induces mouse cognitive impairment and hippocampal neuronal damage through mitophagy suppression via inactivating the AMPK/ULK1/FUNDC1 pathway. (PubMed, Cell Death Discov) - "A mouse NTRK1-knockdown model was established and subjected to pre-treatment with BAY-3827, followed by a behavioral test, Nissl staining, and NeuN immunofluorescence (IF) staining to evaluate the cognitive impairment and hippocampal neuronal damage...Conversely, pre-treatment with O304 and rapamycin abrogated the suppression of mitophagy and the promotion of neuronal damage induced upon NTRK1 silencing. Conclusively, NTRK1 knockdown induces mouse hippocampal neuronal damage through the suppression of mitophagy via inactivating the AMPK/ULK1/FUNDC1 pathway. This finding would provide insight leading to the development of novel strategies for the treatment of cognitive impairment induced due to hippocampal neuronal damage."

Journal • Preclinical • Alzheimer's Disease • Cognitive Disorders • NTRK • NTRK1

First report of Neophysopella vitis causing leaf rust on Parthenocissus semicordata in Guangdong Province, China. (PubMed, Plant Dis) - "The sequences were submitted to NCBI (ITS: OQ991182 OQ991183, LSU: OQ979612 OQ979613), and blastn analyses of ITS and LSU showed 99.81% and 99.84% identity with the sequences from N. vitis (ITS: OQ304336, LSU: OM420266), respectively, found in GenBank...semicordata is often used as an ornamental plant for exterior wall decoration in urban landscaping and court. The occurrence of this disease can lead to the decline of the P. semicordata leaves and the impairment of the plants aesthetically."

Journal

O304 ameliorates hyperglycemia in mice by dually promoting muscle glucose effectiveness and preserving β-cell function. (PubMed, Commun Biol) - "In db/db mice O304 preserves β-cell function by preventing decline in insulin secretion, β-cell mass, and pancreatic insulin content. Thus, as a dual AMPK activator and mitochondrial uncoupler O304 mitigates two central defects of T2D; impaired glucose uptake/utilization and β-cell failure, which today lack effective treatment."

Journal • Preclinical • Cardiomyopathy • Cardiovascular • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

First report of Didymella curtisii causing leaf scorch on spider lily (Hymenocallis littoralis) in China. (PubMed, Plant Dis) - "These three isolates had the same nucleotide sequences, one of which was submitted to NCBI (ITS, OM279485; rpb2, OM304305; LSU, OP800249; tub2, OQ108870)...To our knowledge, this is the first report of leaf scorch on H. littoralis in Yunnan province, China, caused by D. curtisii. The results laid the foundation for epidemiological forecasting and scientific control of this disease."

Journal

Analgesic Effectiveness and Dorsal Root Ganglia Protein Modulation of a Peripheral Adenosine Monophosphate Kinase Alpha Activator (O304) Following Lumbar Disk Puncture in the Mouse. (PubMed, Anesth Analg) - "The direct peripheral AMPK activator O304 reduced allodynia in a dose-dependent manner, and immunoblot studies of the DRG showed that O304 increased p-AMPK and decreased TRPA1, p-ERK1/2, as well as translation factors involved in neuroplasticity. Our findings confirm the role of peripheral AMPKα activation in modulating nociceptive pain."

Journal • Preclinical • Back Pain • Musculoskeletal Pain • Pain • EIF2S1 • EIF4E • GAPDH • mTOR • TRPA1

First Report of Pseudopestalotiopsis theae Causing Leaf Spot on Euonymus japonicus in China. (PubMed, Plant Dis) - "The sequences were deposited in NCBI GenBank YF-24, [ITS; ON204233: TUB2; ON304156: TEF1; ON400075]: YF-5, [ITS; OP379570: TUB2; OP413495: TEF1; OP413496]: YF-13, [ITS; OP379589: TUB2; OP413494: TEF1; OP413497]...This disease is reducing the ornamental value of E. japonicus. Our results will contribute to the prevention and cure of leaf spot disease in E. japonicus."

Journal • Infectious Disease

Isoform Site Specificity Of A Peripheral Adenosine Mono-phosphate Kinase Alpha (ampkÁ) Activator (o304) And Ampk Sirna Transfection Studies In Dorsal Root Ganglia (ASA 2022) - "Our findings confirm the activity of O304 appears to be primarily dependent on the AMPKα2 subunit and to a lesser extent with AMPKα1 subunit of the AMPK heterotrimer."

AMPK • NGF

First report of the root-knot nematode Meloidogyne incognita on Salvia miltiorrhiza Bunge in Henan Province, China. (PubMed, Plant Dis) - "OM304617.1...With the increase of Chinese herbal medicine planting area, plant parasitic nematodes are becoming more and more serious and have become an limiting factor on medicinal plant production, and the yield losses can be as high as 70%. This finding provides important and solid information for growers of Chinese medicinal plants, based on which suitable management action should be taken."

Journal • Cardiovascular

Leaf blast, a new disease on Pennisetum sinese caused by Pyricularia pennisetigena in China. (PubMed, Plant Dis) - "(ITS: OM294657, LSU: OM294656, ACT: OM304642, RPB2: OM304643)...Han et al (2020) reported bacterial leaf blast on king grass while this is first report of P. pennisetigena causing leaf blast. This finding is a warning to prevent and control of this disease and its infectivity to Poaceae plants."

Journal

AMPK Activator O304 Protects Against Kidney Aging Through Promoting Energy Metabolism and Autophagy. (PubMed, Front Pharmacol) - "All these results suggest that O304 has a strong potential to retard aged kidney injury through regulating AMPK-induced multiple pathways. Our results provide an important therapeutic approach to delay kidney aging."

Journal • Fibrosis • Immunology • Renal Disease

First report of powdery mildew caused by Erysiphe euonymicola on wintercreeper (Euonymus fortunei) in China. (PubMed, Plant Dis) - "OM304857)...It could become a threat to the widespread planting of wintercreeper, Similar report has been in Korea (Lee, C. K., et al. 2015)."

Journal

Pan-AMPK activator O304 prevents gene expression changes and remobilisation of histone marks in islets of diet-induced obese mice. (PubMed, Sci Rep) - "Moreover, O304 treatment restored dysfunctional glucose homeostasis as well as expression of key markers associated with β-cell function in mice with already established obesity. Our findings provide preclinical evidence that O304 is a promising therapeutic compound not only for T2D remission but also for restoration of β-cell function following remission of T2D diabetes."

Journal • Preclinical • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

AMPK activator O304 improves metabolic and cardiac function, and exercise capacity in aged mice. (PubMed, Commun Biol) - "These results provide preclinical evidence that O304 mimics the beneficial effects of exercise. Thus, as an exercise mimetic in clinical development, AMPK activator O304 holds great potential to mitigate metabolic dysfunction, and to improve cardiac function and exercise capacity, and hence quality of life in aged individuals."

Journal • Preclinical • Metabolic Disorders

"Betagenon co-founder publishes study demonstrating that pan-AMPK activator O304 acts as an exercise mimetic in aged mice https://t.co/8rMcE40x4h" (@CisionNews)

Preclinical

[VIRTUAL] Peripheral Adenosine Mono-phosphate Activated Kinase Alpha As A Novel Analgesic Target For Chronic Low Back Pain (ASA 2021) - "To create low back pain, mice underwent surgery under general anesthesia consisting of 1.5 % isoflurane (Abbott Laboratories, North Chicago, IL, USA) in oxygen.2 Mice were placed in the dorsolateral position, a povidone iodine USP 10% topical antiseptic solution was applied to the skin and a left lateral abdominal incision approximately 1.5 cm in length made with a #15-blade scalpel. O304, at the dose of 200mg/kg reduced the paw withdrawal hypersensitivity, demonstrating that peripheral AMPK activation can reduce peripheral tissue injury pain in and in vivo model of low back pain in mice."

Anesthesia • Back Pain • Immunology • Lumbar Back Pain • Musculoskeletal Pain • Pain

Peripheral Adenosine Mono-phosphate Activated Kinase Alpha As A Novel Analgesic Target For Chronic Low Back Pain (ASA 2021) - "To create low back pain, mice underwent surgery under general anesthesia consisting of 1.5 % isoflurane (Abbott Laboratories, North Chicago, IL, USA) in oxygen.2 Mice were placed in the dorsolateral position, a povidone iodine USP 10% topical antiseptic solution was applied to the skin and a left lateral abdominal incision approximately 1.5 cm in length made with a #15-blade scalpel. O304, at the dose of 200mg/kg reduced the paw withdrawal hypersensitivity, demonstrating that peripheral AMPK activation can reduce peripheral tissue injury pain in and in vivo model of low back pain in mice."

Anesthesia • Back Pain • Immunology • Lumbar Back Pain • Musculoskeletal Pain • Pain

[VIRTUAL] OS304: Neurogenetics (EAN 2020) - No abstract available

PAN-AMPK activator O304 improves glucose homeostasis and microvascular perfusion in mice and type 2 diabetes patients. (PubMed, JCI Insight) - "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. 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. Thus, O304 exhibits a great potential as a novel drug to treat T2D and associated cardiovascular complications."

Journal

AMP-activated protein kinase (AMPK) activator drugs reduce mechanical allodynia in a mouse model of low back pain. (PubMed, Reg Anesth Pain Med) - "Lumbar disc puncture in mice produces consistent mechanical hypersensitivity, and postinjury treatment with AMPK activator drugs (indirect and direct) reduces the mechanical hypersensitivity."

Journal • Preclinical

Antihyperalgesia effect of AMP-activated protein kinase (AMPK) activators in a mouse model of postoperative pain. (PubMed, Reg Anesth Pain Med) - "Early treatment with the mechanism-specific AMPK activator O304 or the prototype AMPK activator metformin reduces mechanical hypersensitivity in a postoperative pain model in mice. These drugs also normalize the AMPK pathway in the DRG."

Journal • Preclinical