RA123

RA123 is a novel, specific allosteric inhibitor of glutaminase 1 (GLS1) developed by Sanofi. It targets the glutamine metabolism pathway, which tumors often exploit to meet bioenergetic demands in nutrient-poor environments. In preclinical studies, RA123 demonstrated significant anti-tumor activity in multiple myeloma models, specifically the IMiD-resistant and CD38-low RPMI8226 cell line. The drug works by inhibiting the conversion of glutamine to glutamate, leading to a reduction in intracellular glutamate pools and an accumulation of glutamine. Its efficacy has been validated in vivo through dose-dependent tumor growth inhibition and confirmed via [18F]FSPG PET imaging for target engagement.