GSK1521498 / GSK - LARVOL DELTA

Toward a Small-Molecule Antagonist Radioligand for Positron Emission Tomography Imaging of the Mu Opioid Receptor. (PubMed, ACS Chem Neurosci) - "Naloxone was able to reduce [11C]1A binding, though the interactions were not as pronounced as naloxone's ability to displace [11C]carfentanil. These results suggest that GSK1521498 and related congeners are amenable to radioligand design and can offer a safer way to query opioid neurobiology."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Psychiatry

A Small-molecule Antagonist Radiotracer for Positron Emission Tomography Imaging of the Mu Opioid Receptor. (PubMed, bioRxiv) - "Naloxone was able to reduce [ 11 C] 1A binding, though the interactions were not as pronounced as naloxone's ability to displace [ 11 C]carfentanil. These results suggest that GSK1521498 and related congeners are amenable to radioligand design and can offer a safer way to query opioid neurobiology."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Psychiatry

Total-body imaging of mu-opioid receptors with [11C]carfentanil in non-human primates. (PubMed, Eur J Nucl Med Mol Imaging) - "[11C]CFN total-body PET scans could be a useful approach for studying mechanism of action of MOR drugs used in the treatment of acute and chronic opioid use disorder and their effect on the biodistribution of synthetic opioids such as CFN. GSK1521498 could be a potential naloxone alternative to reverse opioid overdose."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Substance Abuse

T cell-mediated tumor killing sensitivity gene signature-based prognostic score for acute myeloid leukemia. (PubMed, Discov Oncol) - "A T-cell mediated killing sensitivity gene-based prognostic score TTKPI showed good accuracy in predicting survival in AML. TTKPI corresponded to functional and immunological features of the tumor microenvironment including checkpoint expression patterns and should be investigated for precision medicine approaches."

Gene Signature • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD4

Small-molecule antagonist radiotracers for positron emission tomography imaging of the mu opioid receptor (ACS-Sp 2024) - "This library is based on MOR antagonist GSK1521498 and was designed to be compatible with metallophotoredox radiomethylation...This represents a paradigm shift towards enabling study of the MOR through safer radiopharmaceuticals. Ongoing medicinal chemistry efforts are aimed at improving ligand affinity."

CNS Disorders • Depression • Mental Retardation • Pain • Psychiatry

Lessons learned from using fMRI in the early clinical development of a mu-opioid receptor antagonist for disorders of compulsive consumption. (PubMed, Psychopharmacology (Berl)) - "In this short review, we summarize data from experimental medicine and early clinical development studies of a mu-opioid receptor antagonist, GSK1521498 developed for disorders of compulsive consumption including binge eating in obesity...While these data highlight the value of fMRI as a biomarker in drug development, its use for making Go/No-go decisions is still faced with challenges given the variability of responses, interpretation of brain activation changes and the limited data linking drug induced changes in brain activity to clinical or behavioural outcome. These challenges need to be addressed to fulfil the promise of fMRI as a tool in clinical drug development."

Clinical • Journal • Review • MRI