GNF-5837 / Novartis, Zhejiang University - LARVOL DELTA

GNF-5837 alleviates intervertebral disc ageing by upregulating glutathione peroxidase 7. (PubMed, Int J Immunopathol Pharmacol) - "Our study demonstrates that GNF-5837 reduced the expression of ageing markers by upregulating GPX7, suggesting it could serve as a potential treatment for IVDD."

Journal • Metabolic Disorders • Oncology • GPX7

GNF-5837 attenuates acute liver injury by inhibiting oxidative stress. (PubMed, Mol Biol Rep) - "Therefore, our research indicates that the small molecule compound GNF-5837 is an oxygen radical scavenger with significant peroxide removal effects, which offer a potential therapeutic approach for cell death caused by imbalances in intracellular oxidative stress levels and provides new insights into the study of acute liver injury."

Journal • Hepatology • Liver Failure

Effects of oral administration of a nonselective Trk inhibitor on lower urinary tract dysfunction in mice with spinal cord injury (AUA 2025) - "Therefore, this study has examined the effects of GNF5837, a nonselective Trk receptor inhibitor, on LUTD as well as nociceptive and mechanosensitive afferent neuronal markers in SCI mice... Trk receptor inhibition could be an effective modality for the treatment of SCI-related neurogenic LUTD such as DO and DSD."

Preclinical • Ataxia • CNS Disorders • Orthopedics • BDNF • NTRK2 • NTRK3 • TRPA1 • TRPV1

Pain mediator NGF improves chondrocyte extracellular matrix synthesis via PI3K/AKT pathway. (PubMed, J Orthop Surg Res) - "Our study identified a potentially beneficial role of NGF at concentrations of 0.5-5 ng/mL in chondrocytes, enhancing extracellular matrix synthesis, with significant involvement of the PI3K/AKT signaling pathway in this process."

Journal • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology • ACAN • NGF • SOX9

Effects of oral administration of nonselective Trk inhibitor on bladder overactivity in rodent models of prostatic inflammation. (PubMed, Prostate) - "The findings of our study suggest that Trk receptor inhibition, which reduced bladder hypersensitivity and inflammatory responses in the prostate, along with a decrease in overexpression of Trk and TRPV1 receptors in sensory pathways, could be an effective treatment strategy for male lower urinary tract symptoms associated with PI and bladder overactivity."

Journal • Preclinical • Immunology • Inflammation • BDNF • CDH1 • NGF • NTRK2 • NTRK3

Catalpol rescues LPS-induced cognitive impairment via inhibition of NF-Κb-regulated neuroinflammation and up-regulation of TrkB-mediated BDNF secretion in mice. (PubMed, J Ethnopharmacol) - "Catalpol alleviates LPS-triggered post-sepsis cognitive impairment by reversing neuroinflammation via blocking the NF-κB pathway, up-regulating neurotrophic factors via the activation of TrkB pathway, and preserving BBB integrity."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Infectious Disease • Inflammation • Septic Shock • BDNF • NTRK2

Receptor-Independent Anti-Ferroptotic Activity of TrkB Modulators. (PubMed, Int J Mol Sci) - "TrkB modulators such as agonist BDNF, antagonist ANA-12, and inhibitor K252a did not affect RSL3-induced ferroptosis sensitivity in primary cortical neurons expressing detectable TrkB receptors. Several other modulators of the TrkB receptor, including agonist 7,8-DHF, activator phenelzine sulphate, and inhibitor GNF-5837, conferred protection against a range of ferroptosis inducers in several immortalised neuronal and non-neuronal cell lines, such as N27 and HT-1080 cells. We found these immortalised cell lines lack detectable TrkB receptor expression, so the anti-ferroptotic activity of these TrkB modulators was most likely due to their inherent radical-trapping antioxidant properties, which should be considered when interpreting their experimental findings. These modulators or their variants could be potential anti-ferroptotic therapeutics for various diseases."

Journal • Alzheimer's Disease • CNS Disorders • NTRK2

Epitope alteration by small molecules and applications in drug discovery. (PubMed, Chem Sci) - "SPEED, applied to an Aβ antibody, led to the discovery of a small molecule, GNF5837, that inhibits Aβ aggregation and another, obatoclax, that binds Aβ plaques and can serve as a fluorescent reporter in brain slices of AD mice. We also found a small molecule that altered the binding between Aβ and auto-antibodies from AD patient serum. SPEED reveals the sensitivity of antibody-epitope interactions to perturbation by small molecules and will have multiple applications in biotechnology and drug discovery."

Journal • Alzheimer's Disease • CNS Disorders • PD-L1