GSK321 / GSK - LARVOL DELTA

From Inhibitors to PET: SAR-Based Development of [18F]SK60 for mIDH1 Imaging. (PubMed, J Med Chem) - "In addition, limited brain uptake was observed by PET suggesting that further structural modifications to reduce lipophilicity might be needed for this structure. The present study led thus to a novel series of dimethylated GSK321 derivatives for further investigation in IDH1R132H-related therapies and PET imaging."

Journal • Oncology • IDH1

Synthesis and evaluation of radiofluorinated GSK321 analogues as candidate radiotracers for imaging mutant IDH1 expression in gliomas (EANM 2024) - "This study resulted in the development of a novel series of fluorinated mIDHR132H inhibitors. Consequently, [18F]SK60 and [18F]SK87 were successfully radiofluorinated. Our preclinical evaluation of [18F]SK60 demonstrated high metabolic stability, limited brain uptake and hepatobiliary excretion in vivo in healthy mice."

Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • IDH1

[18F]SK60: A Novel PET Radioligand for the Imaging of Mutated Isocitrate Dehydrogenase (SNMMI 2024) - " A SAR study was performed on GSK321, a potent mIDH1 inhibitor... Overall, this study resulted in the development of a novel series of fluorinated IDH1-R132H mutation inhibitors. Consequently, [18F]SK60 was successfully developed and evaluated pre-clinically. In general, our results promote the assessment and further modifications of [18F]SK60 for better brain permeation to enhance the non-invasive detection of glioma and other tumors associated with IDH1-R132H mutation."

Acute Myelogenous Leukemia • Biliary Cancer • Brain Cancer • Cholangiocarcinoma • CNS Tumor • Gastrointestinal Cancer • Glioblastoma • Glioma • Hematological Malignancies • Leukemia • Oncology • Sarcoma • Solid Tumor • IDH1

Metabolic reprogramming in the OPA1-deficient cells. (PubMed, Cell Mol Life Sci) - "Prevention of cytosolic glutamine reductive carboxylation by GSK321, an inhibitor of isocitrate dehydrogenase 1 (IDH1), largely repressed lipid synthesis and blocked cell proliferation in OPA1-deficient MEFs. Our data support that, when glucose oxidation failed to support lipogenesis and proliferation in cells with unbalanced mitochondrial fission, OPA1 deficiency stimulated metabolic anaplerosis into glutamine-dependent reductive carboxylation in an IDH1-mediated manner."

Journal • Ocular Inflammation • IDH1